Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
Identifieur interne : 000768 ( Main/Corpus ); précédent : 000767; suivant : 000769Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
Auteurs : Michael A. Van Es ; Helenius J. Schelhaas ; Paul W. J. Van Vught ; Nicola Ticozzi ; Peter M. Andersen ; Ewout J. N. Groen ; Claudia Schulte ; Hylke M. Blauw ; Max Koppers ; Frank P. Diekstra ; Katsumi Fumoto ; Ashley Lyn Leclerc ; Pamela Keagle ; Bastiaan R. Bloem ; Hans Scheffer ; Bart F. L. Van Nuenen ; Marka Van Blitterswijk ; Wouter Van Rheenen ; Anne-Marie Wills ; Patrick P. Lowe ; Guo-Fu Hu ; Wenhao Yu ; Hiroko Kishikawa ; David Wu ; Rebecca D. Folkerth ; Claudio Mariani ; Stefano Goldwurm ; Gianni Pezzoli ; Philip Van Damme ; Robin Lemmens ; Caroline Dahlberg ; Anna Birve ; Rubén Fernández-Santiago ; Stefan Waibel ; Christine Klein ; Markus Weber ; Anneke J. Van Der Kooi ; Marianne De Visser ; Dagmar Verbaan ; Jacobus J. Van Hilten ; Peter Heutink ; Eric A. M. Hennekam ; Edwin Cuppen ; Daniela Berg ; Robert H. Brown Jr ; Vincenzo Silani ; Thomas Gasser ; Albert C. Ludolph ; Wim Robberecht ; Roel A. Ophoff ; Jan H. Veldink ; R. Jeroen Pasterkamp ; Paul I. W. De Bakker ; John E. Landers ; Bart P. Van De Warrenburg ; Leonard H. Van Den BergSource :
- Annals of Neurology [ 0364-5134 ] ; 2011-12.
Abstract
Objective:: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods:: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel‐Haenszel procedure was used to estimate odds ratios. Results:: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10−6 for ALS and p = 4.3 × 10−5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation:: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011;70:964–973
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DOI: 10.1002/ana.22611
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Schelhaas</name><affiliation><mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Vught, Paul W J" sort="Van Vught, Paul W J" uniqKey="Van Vught P" first="Paul W. J." last="Van Vught">Paul W. J. Van Vught</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Ticozzi, Nicola" sort="Ticozzi, Nicola" uniqKey="Ticozzi N" first="Nicola" last="Ticozzi">Nicola Ticozzi</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Andersen, Peter M" sort="Andersen, Peter M" uniqKey="Andersen P" first="Peter M." last="Andersen">Peter M. Andersen</name><affiliation><mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Groen, Ewout J N" sort="Groen, Ewout J N" uniqKey="Groen E" first="Ewout J. N." last="Groen">Ewout J. N. Groen</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Schulte, Claudia" sort="Schulte, Claudia" uniqKey="Schulte C" first="Claudia" last="Schulte">Claudia Schulte</name><affiliation><mods:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Blauw, Hylke M" sort="Blauw, Hylke M" uniqKey="Blauw H" first="Hylke M." last="Blauw">Hylke M. Blauw</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Koppers, Max" sort="Koppers, Max" uniqKey="Koppers M" first="Max" last="Koppers">Max Koppers</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Diekstra, Frank P" sort="Diekstra, Frank P" uniqKey="Diekstra F" first="Frank P." last="Diekstra">Frank P. Diekstra</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Fumoto, Katsumi" sort="Fumoto, Katsumi" uniqKey="Fumoto K" first="Katsumi" last="Fumoto">Katsumi Fumoto</name><affiliation><mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Leclerc, Ashley Lyn" sort="Leclerc, Ashley Lyn" uniqKey="Leclerc A" first="Ashley Lyn" last="Leclerc">Ashley Lyn Leclerc</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Keagle, Pamela" sort="Keagle, Pamela" uniqKey="Keagle P" first="Pamela" last="Keagle">Pamela Keagle</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Bloem, Bastiaan R" sort="Bloem, Bastiaan R" uniqKey="Bloem B" first="Bastiaan R." last="Bloem">Bastiaan R. Bloem</name><affiliation><mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Scheffer, Hans" sort="Scheffer, Hans" uniqKey="Scheffer H" first="Hans" last="Scheffer">Hans Scheffer</name><affiliation><mods:affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Nuenen, Bart F L" sort="Van Nuenen, Bart F L" uniqKey="Van Nuenen B" first="Bart F. L." last="Van Nuenen">Bart F. L. Van Nuenen</name><affiliation><mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Blitterswijk, Marka" sort="Van Blitterswijk, Marka" uniqKey="Van Blitterswijk M" first="Marka" last="Van Blitterswijk">Marka Van Blitterswijk</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Rheenen, Wouter" sort="Van Rheenen, Wouter" uniqKey="Van Rheenen W" first="Wouter" last="Van Rheenen">Wouter Van Rheenen</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Wills, Anne Arie" sort="Wills, Anne Arie" uniqKey="Wills A" first="Anne-Marie" last="Wills">Anne-Marie Wills</name><affiliation><mods:affiliation>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Lowe, Patrick P" sort="Lowe, Patrick P" uniqKey="Lowe P" first="Patrick P." last="Lowe">Patrick P. Lowe</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Hu, Guo U" sort="Hu, Guo U" uniqKey="Hu G" first="Guo-Fu" last="Hu">Guo-Fu Hu</name><affiliation><mods:affiliation>Department of Pathology, Harvard Medical School, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Yu, Wenhao" sort="Yu, Wenhao" uniqKey="Yu W" first="Wenhao" last="Yu">Wenhao Yu</name><affiliation><mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Kishikawa, Hiroko" sort="Kishikawa, Hiroko" uniqKey="Kishikawa H" first="Hiroko" last="Kishikawa">Hiroko Kishikawa</name><affiliation><mods:affiliation>Department of Pathology, Harvard Medical School, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Wu, David" sort="Wu, David" uniqKey="Wu D" first="David" last="Wu">David Wu</name><affiliation><mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Folkerth, Rebecca D" sort="Folkerth, Rebecca D" uniqKey="Folkerth R" first="Rebecca D." last="Folkerth">Rebecca D. Folkerth</name><affiliation><mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Mariani, Claudio" sort="Mariani, Claudio" uniqKey="Mariani C" first="Claudio" last="Mariani">Claudio Mariani</name><affiliation><mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Goldwurm, Stefano" sort="Goldwurm, Stefano" uniqKey="Goldwurm S" first="Stefano" last="Goldwurm">Stefano Goldwurm</name><affiliation><mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Pezzoli, Gianni" sort="Pezzoli, Gianni" uniqKey="Pezzoli G" first="Gianni" last="Pezzoli">Gianni Pezzoli</name><affiliation><mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Van Damme, Philip" sort="Van Damme, Philip" uniqKey="Van Damme P" first="Philip" last="Van Damme">Philip Van Damme</name><affiliation><mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Lemmens, Robin" sort="Lemmens, Robin" uniqKey="Lemmens R" first="Robin" last="Lemmens">Robin Lemmens</name><affiliation><mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Dahlberg, Caroline" sort="Dahlberg, Caroline" uniqKey="Dahlberg C" first="Caroline" last="Dahlberg">Caroline Dahlberg</name><affiliation><mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Birve, Anna" sort="Birve, Anna" uniqKey="Birve A" first="Anna" last="Birve">Anna Birve</name><affiliation><mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Fernandez Antiago, Ruben" sort="Fernandez Antiago, Ruben" uniqKey="Fernandez Antiago R" first="Rubén" last="Fernández-Santiago">Rubén Fernández-Santiago</name><affiliation><mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Waibel, Stefan" sort="Waibel, Stefan" uniqKey="Waibel S" first="Stefan" last="Waibel">Stefan Waibel</name><affiliation><mods:affiliation>Department of Neurology, University of Ulm, Ulm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation><mods:affiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Weber, Markus" sort="Weber, Markus" uniqKey="Weber M" first="Markus" last="Weber">Markus Weber</name><affiliation><mods:affiliation>Neuromuscular Diseases Unit, Kantonspital St Gallen, St Gallen, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Van Der Kooi, Anneke J" sort="Van Der Kooi, Anneke J" uniqKey="Van Der Kooi A" first="Anneke J." last="Van Der Kooi">Anneke J. Van Der Kooi</name><affiliation><mods:affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="De Visser, Marianne" sort="De Visser, Marianne" uniqKey="De Visser M" first="Marianne" last="De Visser">Marianne De Visser</name><affiliation><mods:affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name><affiliation><mods:affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Hilten, Jacobus J" sort="Van Hilten, Jacobus J" uniqKey="Van Hilten J" first="Jacobus J." last="Van Hilten">Jacobus J. Van Hilten</name><affiliation><mods:affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name><affiliation><mods:affiliation>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Hennekam, Eric A M" sort="Hennekam, Eric A M" uniqKey="Hennekam E" first="Eric A. M." last="Hennekam">Eric A. M. Hennekam</name><affiliation><mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Cuppen, Edwin" sort="Cuppen, Edwin" uniqKey="Cuppen E" first="Edwin" last="Cuppen">Edwin Cuppen</name><affiliation><mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Berg, Daniela" sort="Berg, Daniela" uniqKey="Berg D" first="Daniela" last="Berg">Daniela Berg</name><affiliation><mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Brown Jr, Robert H" sort="Brown Jr, Robert H" uniqKey="Brown Jr R" first="Robert H." last="Brown Jr">Robert H. Brown Jr</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Silani, Vincenzo" sort="Silani, Vincenzo" uniqKey="Silani V" first="Vincenzo" last="Silani">Vincenzo Silani</name><affiliation><mods:affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Milan Medical School, “Dino Ferrari” Center, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><affiliation><mods:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Ludolph, Albert C" sort="Ludolph, Albert C" uniqKey="Ludolph A" first="Albert C." last="Ludolph">Albert C. Ludolph</name><affiliation><mods:affiliation>Department of Neurology, University of Ulm, Ulm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Robberecht, Wim" sort="Robberecht, Wim" uniqKey="Robberecht W" first="Wim" last="Robberecht">Wim Robberecht</name><affiliation><mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Ophoff, Roel A" sort="Ophoff, Roel A" uniqKey="Ophoff R" first="Roel A." last="Ophoff">Roel A. Ophoff</name><affiliation><mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>University of California at Los Angeles Center for Neurobehavioral Genetics, Los Angeles, CA</mods:affiliation></affiliation></author><author><name sortKey="Veldink, Jan H" sort="Veldink, Jan H" uniqKey="Veldink J" first="Jan H." last="Veldink">Jan H. Veldink</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Pasterkamp, R Jeroen" sort="Pasterkamp, R Jeroen" uniqKey="Pasterkamp R" first="R. Jeroen" last="Pasterkamp">R. Jeroen Pasterkamp</name><affiliation><mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="De Bakker, Paul I W" sort="De Bakker, Paul I W" uniqKey="De Bakker P" first="Paul I. W." last="De Bakker">Paul I. W. De Bakker</name><affiliation><mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA</mods:affiliation></affiliation><affiliation><mods:affiliation>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA</mods:affiliation></affiliation><affiliation><mods:affiliation>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Landers, John E" sort="Landers, John E" uniqKey="Landers J" first="John E." last="Landers">John E. Landers</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Van De Warrenburg, Bart P" sort="Van De Warrenburg, Bart P" uniqKey="Van De Warrenburg B" first="Bart P." last="Van De Warrenburg">Bart P. Van De Warrenburg</name><affiliation><mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Den Berg, Leonard H" sort="Van Den Berg, Leonard H" uniqKey="Van Den Berg L" first="Leonard H." last="Van Den Berg">Leonard H. Van Den Berg</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1104402D2CD5B78610B101FB2326A7D93EC038A3</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1002/ana.22611</idno><idno type="url">https://api.istex.fr/document/1104402D2CD5B78610B101FB2326A7D93EC038A3/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000768</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis</title><author><name sortKey="Van Es, Michael A" sort="Van Es, Michael A" uniqKey="Van Es M" first="Michael A." last="Van Es">Michael A. Van Es</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Schelhaas, Helenius J" sort="Schelhaas, Helenius J" uniqKey="Schelhaas H" first="Helenius J." last="Schelhaas">Helenius J. Schelhaas</name><affiliation><mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Vught, Paul W J" sort="Van Vught, Paul W J" uniqKey="Van Vught P" first="Paul W. J." last="Van Vught">Paul W. J. Van Vught</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Ticozzi, Nicola" sort="Ticozzi, Nicola" uniqKey="Ticozzi N" first="Nicola" last="Ticozzi">Nicola Ticozzi</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Andersen, Peter M" sort="Andersen, Peter M" uniqKey="Andersen P" first="Peter M." last="Andersen">Peter M. Andersen</name><affiliation><mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Groen, Ewout J N" sort="Groen, Ewout J N" uniqKey="Groen E" first="Ewout J. N." last="Groen">Ewout J. N. Groen</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Schulte, Claudia" sort="Schulte, Claudia" uniqKey="Schulte C" first="Claudia" last="Schulte">Claudia Schulte</name><affiliation><mods:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Blauw, Hylke M" sort="Blauw, Hylke M" uniqKey="Blauw H" first="Hylke M." last="Blauw">Hylke M. Blauw</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Koppers, Max" sort="Koppers, Max" uniqKey="Koppers M" first="Max" last="Koppers">Max Koppers</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Diekstra, Frank P" sort="Diekstra, Frank P" uniqKey="Diekstra F" first="Frank P." last="Diekstra">Frank P. Diekstra</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Fumoto, Katsumi" sort="Fumoto, Katsumi" uniqKey="Fumoto K" first="Katsumi" last="Fumoto">Katsumi Fumoto</name><affiliation><mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Leclerc, Ashley Lyn" sort="Leclerc, Ashley Lyn" uniqKey="Leclerc A" first="Ashley Lyn" last="Leclerc">Ashley Lyn Leclerc</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Keagle, Pamela" sort="Keagle, Pamela" uniqKey="Keagle P" first="Pamela" last="Keagle">Pamela Keagle</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Bloem, Bastiaan R" sort="Bloem, Bastiaan R" uniqKey="Bloem B" first="Bastiaan R." last="Bloem">Bastiaan R. Bloem</name><affiliation><mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Scheffer, Hans" sort="Scheffer, Hans" uniqKey="Scheffer H" first="Hans" last="Scheffer">Hans Scheffer</name><affiliation><mods:affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Nuenen, Bart F L" sort="Van Nuenen, Bart F L" uniqKey="Van Nuenen B" first="Bart F. L." last="Van Nuenen">Bart F. L. Van Nuenen</name><affiliation><mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Blitterswijk, Marka" sort="Van Blitterswijk, Marka" uniqKey="Van Blitterswijk M" first="Marka" last="Van Blitterswijk">Marka Van Blitterswijk</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Rheenen, Wouter" sort="Van Rheenen, Wouter" uniqKey="Van Rheenen W" first="Wouter" last="Van Rheenen">Wouter Van Rheenen</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Wills, Anne Arie" sort="Wills, Anne Arie" uniqKey="Wills A" first="Anne-Marie" last="Wills">Anne-Marie Wills</name><affiliation><mods:affiliation>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Lowe, Patrick P" sort="Lowe, Patrick P" uniqKey="Lowe P" first="Patrick P." last="Lowe">Patrick P. Lowe</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Hu, Guo U" sort="Hu, Guo U" uniqKey="Hu G" first="Guo-Fu" last="Hu">Guo-Fu Hu</name><affiliation><mods:affiliation>Department of Pathology, Harvard Medical School, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Yu, Wenhao" sort="Yu, Wenhao" uniqKey="Yu W" first="Wenhao" last="Yu">Wenhao Yu</name><affiliation><mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Kishikawa, Hiroko" sort="Kishikawa, Hiroko" uniqKey="Kishikawa H" first="Hiroko" last="Kishikawa">Hiroko Kishikawa</name><affiliation><mods:affiliation>Department of Pathology, Harvard Medical School, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Wu, David" sort="Wu, David" uniqKey="Wu D" first="David" last="Wu">David Wu</name><affiliation><mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Folkerth, Rebecca D" sort="Folkerth, Rebecca D" uniqKey="Folkerth R" first="Rebecca D." last="Folkerth">Rebecca D. Folkerth</name><affiliation><mods:affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Mariani, Claudio" sort="Mariani, Claudio" uniqKey="Mariani C" first="Claudio" last="Mariani">Claudio Mariani</name><affiliation><mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Goldwurm, Stefano" sort="Goldwurm, Stefano" uniqKey="Goldwurm S" first="Stefano" last="Goldwurm">Stefano Goldwurm</name><affiliation><mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Pezzoli, Gianni" sort="Pezzoli, Gianni" uniqKey="Pezzoli G" first="Gianni" last="Pezzoli">Gianni Pezzoli</name><affiliation><mods:affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Van Damme, Philip" sort="Van Damme, Philip" uniqKey="Van Damme P" first="Philip" last="Van Damme">Philip Van Damme</name><affiliation><mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Lemmens, Robin" sort="Lemmens, Robin" uniqKey="Lemmens R" first="Robin" last="Lemmens">Robin Lemmens</name><affiliation><mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Dahlberg, Caroline" sort="Dahlberg, Caroline" uniqKey="Dahlberg C" first="Caroline" last="Dahlberg">Caroline Dahlberg</name><affiliation><mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Birve, Anna" sort="Birve, Anna" uniqKey="Birve A" first="Anna" last="Birve">Anna Birve</name><affiliation><mods:affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Fernandez Antiago, Ruben" sort="Fernandez Antiago, Ruben" uniqKey="Fernandez Antiago R" first="Rubén" last="Fernández-Santiago">Rubén Fernández-Santiago</name><affiliation><mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Waibel, Stefan" sort="Waibel, Stefan" uniqKey="Waibel S" first="Stefan" last="Waibel">Stefan Waibel</name><affiliation><mods:affiliation>Department of Neurology, University of Ulm, Ulm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation><mods:affiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Weber, Markus" sort="Weber, Markus" uniqKey="Weber M" first="Markus" last="Weber">Markus Weber</name><affiliation><mods:affiliation>Neuromuscular Diseases Unit, Kantonspital St Gallen, St Gallen, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Van Der Kooi, Anneke J" sort="Van Der Kooi, Anneke J" uniqKey="Van Der Kooi A" first="Anneke J." last="Van Der Kooi">Anneke J. Van Der Kooi</name><affiliation><mods:affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="De Visser, Marianne" sort="De Visser, Marianne" uniqKey="De Visser M" first="Marianne" last="De Visser">Marianne De Visser</name><affiliation><mods:affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name><affiliation><mods:affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Hilten, Jacobus J" sort="Van Hilten, Jacobus J" uniqKey="Van Hilten J" first="Jacobus J." last="Van Hilten">Jacobus J. Van Hilten</name><affiliation><mods:affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name><affiliation><mods:affiliation>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Hennekam, Eric A M" sort="Hennekam, Eric A M" uniqKey="Hennekam E" first="Eric A. M." last="Hennekam">Eric A. M. Hennekam</name><affiliation><mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Cuppen, Edwin" sort="Cuppen, Edwin" uniqKey="Cuppen E" first="Edwin" last="Cuppen">Edwin Cuppen</name><affiliation><mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Berg, Daniela" sort="Berg, Daniela" uniqKey="Berg D" first="Daniela" last="Berg">Daniela Berg</name><affiliation><mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Brown Jr, Robert H" sort="Brown Jr, Robert H" uniqKey="Brown Jr R" first="Robert H." last="Brown Jr">Robert H. Brown Jr</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Silani, Vincenzo" sort="Silani, Vincenzo" uniqKey="Silani V" first="Vincenzo" last="Silani">Vincenzo Silani</name><affiliation><mods:affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Milan Medical School, “Dino Ferrari” Center, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><affiliation><mods:affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Ludolph, Albert C" sort="Ludolph, Albert C" uniqKey="Ludolph A" first="Albert C." last="Ludolph">Albert C. Ludolph</name><affiliation><mods:affiliation>Department of Neurology, University of Ulm, Ulm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Robberecht, Wim" sort="Robberecht, Wim" uniqKey="Robberecht W" first="Wim" last="Robberecht">Wim Robberecht</name><affiliation><mods:affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Ophoff, Roel A" sort="Ophoff, Roel A" uniqKey="Ophoff R" first="Roel A." last="Ophoff">Roel A. Ophoff</name><affiliation><mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>University of California at Los Angeles Center for Neurobehavioral Genetics, Los Angeles, CA</mods:affiliation></affiliation></author><author><name sortKey="Veldink, Jan H" sort="Veldink, Jan H" uniqKey="Veldink J" first="Jan H." last="Veldink">Jan H. Veldink</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Pasterkamp, R Jeroen" sort="Pasterkamp, R Jeroen" uniqKey="Pasterkamp R" first="R. Jeroen" last="Pasterkamp">R. Jeroen Pasterkamp</name><affiliation><mods:affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="De Bakker, Paul I W" sort="De Bakker, Paul I W" uniqKey="De Bakker P" first="Paul I. W." last="De Bakker">Paul I. W. De Bakker</name><affiliation><mods:affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA</mods:affiliation></affiliation><affiliation><mods:affiliation>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA</mods:affiliation></affiliation><affiliation><mods:affiliation>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Landers, John E" sort="Landers, John E" uniqKey="Landers J" first="John E." last="Landers">John E. Landers</name><affiliation><mods:affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</mods:affiliation></affiliation></author><author><name sortKey="Van De Warrenburg, Bart P" sort="Van De Warrenburg, Bart P" uniqKey="Van De Warrenburg B" first="Bart P." last="Van De Warrenburg">Bart P. Van De Warrenburg</name><affiliation><mods:affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Van Den Berg, Leonard H" sort="Van Den Berg, Leonard H" uniqKey="Van Den Berg L" first="Leonard H." last="Van Den Berg">Leonard H. Van Den Berg</name><affiliation><mods:affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-12">2011-12</date><biblScope unit="volume">70</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="964">964</biblScope><biblScope unit="page" to="973">973</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">1104402D2CD5B78610B101FB2326A7D93EC038A3</idno><idno type="DOI">10.1002/ana.22611</idno><idno type="ArticleID">ANA22611</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective:: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods:: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel‐Haenszel procedure was used to estimate odds ratios. Results:: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10−6 for ALS and p = 4.3 × 10−5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation:: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011;70:964–973</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Michael A. van Es MD, PhD</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Helenius J. Schelhaas MD, PhD</name><affiliations><json:string>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</json:string></affiliations></json:item><json:item><name>Paul W. J. van Vught PhD</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Nicola Ticozzi MD</name><affiliations><json:string>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</json:string><json:string>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</json:string></affiliations></json:item><json:item><name>Peter M. Andersen MD, PhD</name><affiliations><json:string>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</json:string></affiliations></json:item><json:item><name>Ewout J. N. Groen MSc</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Claudia Schulte MD</name><affiliations><json:string>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>Hylke M. Blauw MD</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Max Koppers MSc</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Frank P. Diekstra MD</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Katsumi Fumoto PhD</name><affiliations><json:string>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Ashley Lyn LeClerc BA</name><affiliations><json:string>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</json:string></affiliations></json:item><json:item><name>Pamela Keagle BS</name><affiliations><json:string>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</json:string></affiliations></json:item><json:item><name>Bastiaan R. Bloem MD, PhD</name><affiliations><json:string>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</json:string></affiliations></json:item><json:item><name>Hans Scheffer MD, PhD</name><affiliations><json:string>Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands</json:string></affiliations></json:item><json:item><name>Bart F. L. van Nuenen MD</name><affiliations><json:string>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</json:string></affiliations></json:item><json:item><name>Marka van Blitterswijk MD</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Wouter van Rheenen MD</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Anne‐Marie Wills MD</name><affiliations><json:string>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</json:string></affiliations></json:item><json:item><name>Patrick P. Lowe</name><affiliations><json:string>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</json:string></affiliations></json:item><json:item><name>Guo‐fu Hu PhD</name><affiliations><json:string>Department of Pathology, Harvard Medical School, Boston, MA</json:string></affiliations></json:item><json:item><name>Wenhao Yu PhD</name><affiliations><json:string>Department of Pathology, Brigham and Women's Hospital, Boston, MA</json:string></affiliations></json:item><json:item><name>Hiroko Kishikawa PhD</name><affiliations><json:string>Department of Pathology, Harvard Medical School, Boston, MA</json:string></affiliations></json:item><json:item><name>David Wu MD, PhD</name><affiliations><json:string>Department of Pathology, Brigham and Women's Hospital, Boston, MA</json:string></affiliations></json:item><json:item><name>Rebecca D. Folkerth MD</name><affiliations><json:string>Department of Pathology, Brigham and Women's Hospital, Boston, MA</json:string></affiliations></json:item><json:item><name>Claudio Mariani MD</name><affiliations><json:string>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</json:string></affiliations></json:item><json:item><name>Stefano Goldwurm MD</name><affiliations><json:string>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</json:string></affiliations></json:item><json:item><name>Gianni Pezzoli MD</name><affiliations><json:string>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</json:string></affiliations></json:item><json:item><name>Philip Van Damme MD, PhD</name><affiliations><json:string>Experimental Neurology, University of Leuven, Leuven, Belgium</json:string><json:string>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</json:string><json:string>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</json:string></affiliations></json:item><json:item><name>Robin Lemmens MD, PhD</name><affiliations><json:string>Experimental Neurology, University of Leuven, Leuven, Belgium</json:string><json:string>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</json:string><json:string>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</json:string></affiliations></json:item><json:item><name>Caroline Dahlberg MD</name><affiliations><json:string>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</json:string></affiliations></json:item><json:item><name>Anna Birve PhD</name><affiliations><json:string>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</json:string></affiliations></json:item><json:item><name>Rubén Fernández‐Santiago PhD</name><affiliations><json:string>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</json:string><json:string>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain</json:string><json:string>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>Stefan Waibel MD</name><affiliations><json:string>Department of Neurology, University of Ulm, Ulm, Germany</json:string></affiliations></json:item><json:item><name>Christine Klein MD, PhD</name><affiliations><json:string>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Markus Weber MD, PhD</name><affiliations><json:string>Neuromuscular Diseases Unit, Kantonspital St Gallen, St Gallen, Switzerland</json:string></affiliations></json:item><json:item><name>Anneke J. van der Kooi MD, PhD</name><affiliations><json:string>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</json:string></affiliations></json:item><json:item><name>Marianne de Visser MD, PhD</name><affiliations><json:string>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</json:string></affiliations></json:item><json:item><name>Dagmar Verbaan MD</name><affiliations><json:string>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</json:string></affiliations></json:item><json:item><name>Jacobus J. van Hilten MD, PhD</name><affiliations><json:string>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</json:string></affiliations></json:item><json:item><name>Peter Heutink PhD</name><affiliations><json:string>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam, the Netherlands</json:string></affiliations></json:item><json:item><name>Eric A. M. Hennekam PhD</name><affiliations><json:string>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Edwin Cuppen PhD</name><affiliations><json:string>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</json:string><json:string>Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Daniela Berg MD</name><affiliations><json:string>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Robert H. Brown Jr MD, PhD</name><affiliations><json:string>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</json:string></affiliations></json:item><json:item><name>Vincenzo Silani MD</name><affiliations><json:string>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</json:string><json:string>Department of Neurology, University of Milan Medical School, “Dino Ferrari” Center, Milan, Italy</json:string></affiliations></json:item><json:item><name>Thomas Gasser MD</name><affiliations><json:string>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>Albert C. Ludolph MD, PhD</name><affiliations><json:string>Department of Neurology, University of Ulm, Ulm, Germany</json:string></affiliations></json:item><json:item><name>Wim Robberecht MD, PhD</name><affiliations><json:string>Experimental Neurology, University of Leuven, Leuven, Belgium</json:string><json:string>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</json:string><json:string>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</json:string></affiliations></json:item><json:item><name>Roel A. Ophoff PhD</name><affiliations><json:string>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</json:string><json:string>University of California at Los Angeles Center for Neurobehavioral Genetics, Los Angeles, CA</json:string></affiliations></json:item><json:item><name>Jan H. Veldink MD, PhD</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>R. Jeroen Pasterkamp PhD</name><affiliations><json:string>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Paul I. W. de Bakker PhD</name><affiliations><json:string>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</json:string><json:string>Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA</json:string><json:string>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA</json:string><json:string>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>John E. Landers PhD</name><affiliations><json:string>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</json:string></affiliations></json:item><json:item><name>Bart P. van de Warrenburg MD, PhD</name><affiliations><json:string>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</json:string><json:string>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</json:string></affiliations></json:item><json:item><name>Leonard H. van den Berg MD, PhD</name><affiliations><json:string>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</json:string><json:string>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</json:string></affiliations></json:item></author><articleId><json:string>ANA22611</json:string></articleId><language><json:string>eng</json:string></language><abstract>Objective:: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods:: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel‐Haenszel procedure was used to estimate odds ratios. Results:: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10−6 for ALS and p = 4.3 × 10−5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation:: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011;70:964–973</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 801 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1556</abstractCharCount><pdfWordCount>5494</pdfWordCount><pdfCharCount>36907</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>252</abstractWordCount></qualityIndicators><title>Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis</title><genre><json:string>article</json:string></genre><host><volume>70</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>10</total><last>973</last><first>964</first></pages><issn><json:string>0364-5134</json:string></issn><issue>6</issue><subject><json:item><value>Original Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8249</json:string></eissn><title>Annals of Neurology</title><doi><json:string>10.1002/(ISSN)1531-8249</json:string></doi></host><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1002/ana.22611</json:string></doi><id>1104402D2CD5B78610B101FB2326A7D93EC038A3</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/1104402D2CD5B78610B101FB2326A7D93EC038A3/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/1104402D2CD5B78610B101FB2326A7D93EC038A3/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/1104402D2CD5B78610B101FB2326A7D93EC038A3/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2011</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis</title><author><persName><forename type="first">Michael A.</forename><surname>van Es</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Helenius J.</forename><surname>Schelhaas</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</affiliation></author><author><persName><forename type="first">Paul W. J.</forename><surname>van Vught</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Nicola</forename><surname>Ticozzi</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation><affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</affiliation></author><author><persName><forename type="first">Peter M.</forename><surname>Andersen</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</affiliation></author><author><persName><forename type="first">Ewout J. N.</forename><surname>Groen</surname></persName><roleName type="degree">MSc</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Claudia</forename><surname>Schulte</surname></persName><roleName type="degree">MD</roleName><affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</affiliation></author><author><persName><forename type="first">Hylke M.</forename><surname>Blauw</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Max</forename><surname>Koppers</surname></persName><roleName type="degree">MSc</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Frank P.</forename><surname>Diekstra</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Katsumi</forename><surname>Fumoto</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Ashley Lyn</forename><surname>LeClerc</surname></persName><roleName type="degree">BA</roleName><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation></author><author><persName><forename type="first">Pamela</forename><surname>Keagle</surname></persName><roleName type="degree">BS</roleName><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation></author><author><persName><forename type="first">Bastiaan R.</forename><surname>Bloem</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</affiliation></author><author><persName><forename type="first">Hans</forename><surname>Scheffer</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands</affiliation></author><author><persName><forename type="first">Bart F. L.</forename><surname>van Nuenen</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</affiliation></author><author><persName><forename type="first">Marka</forename><surname>van Blitterswijk</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Wouter</forename><surname>van Rheenen</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Anne‐Marie</forename><surname>Wills</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</affiliation></author><author><persName><forename type="first">Patrick P.</forename><surname>Lowe</surname></persName><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation></author><author><persName><forename type="first">Guo‐fu</forename><surname>Hu</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Pathology, Harvard Medical School, Boston, MA</affiliation></author><author><persName><forename type="first">Wenhao</forename><surname>Yu</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</affiliation></author><author><persName><forename type="first">Hiroko</forename><surname>Kishikawa</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Pathology, Harvard Medical School, Boston, MA</affiliation></author><author><persName><forename type="first">David</forename><surname>Wu</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</affiliation></author><author><persName><forename type="first">Rebecca D.</forename><surname>Folkerth</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</affiliation></author><author><persName><forename type="first">Claudio</forename><surname>Mariani</surname></persName><roleName type="degree">MD</roleName><affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</affiliation></author><author><persName><forename type="first">Stefano</forename><surname>Goldwurm</surname></persName><roleName type="degree">MD</roleName><affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</affiliation></author><author><persName><forename type="first">Gianni</forename><surname>Pezzoli</surname></persName><roleName type="degree">MD</roleName><affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</affiliation></author><author><persName><forename type="first">Philip</forename><surname>Van Damme</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</affiliation><affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</affiliation><affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</affiliation></author><author><persName><forename type="first">Robin</forename><surname>Lemmens</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</affiliation><affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</affiliation><affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</affiliation></author><author><persName><forename type="first">Caroline</forename><surname>Dahlberg</surname></persName><roleName type="degree">MD</roleName><affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</affiliation></author><author><persName><forename type="first">Anna</forename><surname>Birve</surname></persName><roleName type="degree">PhD</roleName><affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</affiliation></author><author><persName><forename type="first">Rubén</forename><surname>Fernández‐Santiago</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain</affiliation><affiliation>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen, Germany</affiliation></author><author><persName><forename type="first">Stefan</forename><surname>Waibel</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Ulm, Ulm, Germany</affiliation></author><author><persName><forename type="first">Christine</forename><surname>Klein</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Markus</forename><surname>Weber</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Neuromuscular Diseases Unit, Kantonspital St Gallen, St Gallen, Switzerland</affiliation></author><author><persName><forename type="first">Anneke J.</forename><surname>van der Kooi</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</affiliation></author><author><persName><forename type="first">Marianne</forename><surname>de Visser</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</affiliation></author><author><persName><forename type="first">Dagmar</forename><surname>Verbaan</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</affiliation></author><author><persName><forename type="first">Jacobus J.</forename><surname>van Hilten</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</affiliation></author><author><persName><forename type="first">Peter</forename><surname>Heutink</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam, the Netherlands</affiliation></author><author><persName><forename type="first">Eric A. M.</forename><surname>Hennekam</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Edwin</forename><surname>Cuppen</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Daniela</forename><surname>Berg</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Robert H.</forename><surname>Brown Jr</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation></author><author><persName><forename type="first">Vincenzo</forename><surname>Silani</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</affiliation><affiliation>Department of Neurology, University of Milan Medical School, “Dino Ferrari” Center, Milan, Italy</affiliation></author><author><persName><forename type="first">Thomas</forename><surname>Gasser</surname></persName><roleName type="degree">MD</roleName><affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</affiliation></author><author><persName><forename type="first">Albert C.</forename><surname>Ludolph</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, University of Ulm, Ulm, Germany</affiliation></author><author><persName><forename type="first">Wim</forename><surname>Robberecht</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</affiliation><affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</affiliation><affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</affiliation></author><author><persName><forename type="first">Roel A.</forename><surname>Ophoff</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>University of California at Los Angeles Center for Neurobehavioral Genetics, Los Angeles, CA</affiliation></author><author><persName><forename type="first">Jan H.</forename><surname>Veldink</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">R. Jeroen</forename><surname>Pasterkamp</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Paul I. W.</forename><surname>de Bakker</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA</affiliation><affiliation>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA</affiliation><affiliation>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">John E.</forename><surname>Landers</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation></author><author><persName><forename type="first">Bart P.</forename><surname>van de Warrenburg</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</affiliation><affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</affiliation></author><author><persName><forename type="first">Leonard H.</forename><surname>van den Berg</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-12"></date><biblScope unit="volume">70</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="964">964</biblScope><biblScope unit="page" to="973">973</biblScope></imprint></monogr><idno type="istex">1104402D2CD5B78610B101FB2326A7D93EC038A3</idno><idno type="DOI">10.1002/ana.22611</idno><idno type="ArticleID">ANA22611</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Objective:: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods:: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel‐Haenszel procedure was used to estimate odds ratios. Results:: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10−6 for ALS and p = 4.3 × 10−5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation:: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011;70:964–973</p></abstract><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Original Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2011-05-21">Received</change><change when="2011-08-12">Registration</change><change when="2011-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/1104402D2CD5B78610B101FB2326A7D93EC038A3/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8249</doi><issn type="print">0364-5134</issn><issn type="electronic">1531-8249</issn><idGroup><id type="product" value="ANA"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="ANNALS OF NEUROLOGY">Annals of Neurology</title><title type="short">Ann Neurol.</title></titleGroup></publicationMeta><publicationMeta level="part" position="60"><doi origin="wiley" registered="yes">10.1002/ana.v70.6</doi><numberingGroup><numbering type="journalVolume" number="70">70</numbering><numbering type="journalIssue">6</numbering></numberingGroup><coverDate startDate="2011-12">December 2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="150" status="forIssue"><doi origin="wiley" registered="yes">10.1002/ana.22611</doi><idGroup><id type="unit" value="ANA22611"></id></idGroup><countGroup><count type="pageTotal" number="10"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="publisher">Copyright © 2011 American Neurological Association</copyright><eventGroup><event type="manuscriptReceived" date="2011-05-21"></event><event type="manuscriptRevised" date="2011-07-20"></event><event type="manuscriptAccepted" date="2011-08-12"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:3.0.1 mode:FullText" date="2012-02-02"></event><event type="publishedOnlineAccepted" date="2011-08-17"></event><event type="publishedOnlineFinalForm" date="2011-12-21"></event><event type="firstOnline" date="2011-12-21"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-03"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">964</numbering><numbering type="pageLast">973</numbering></numberingGroup><correspondenceTo><lineatedText><line>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the Netherlands</line><line>Leonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</line></lineatedText></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA22611.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="3"></count><count type="referenceTotal" number="50"></count><count type="wordTotal" number="6360"></count></countGroup><titleGroup><title type="main" xml:lang="en">Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis</title><title type="short" xml:lang="en">Angiogenin in PD and ALS</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Michael A.</givenNames><familyName>van Es</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Helenius J.</givenNames><familyName>Schelhaas</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Paul W. 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W.</givenNames><familyName>de Bakker</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au54" creatorRole="author" affiliationRef="#af3"><personName><givenNames>John E.</givenNames><familyName>Landers</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au55" creatorRole="author" affiliationRef="#af2" corresponding="yes"><personName><givenNames>Bart P.</givenNames><familyName>van de Warrenburg</familyName><degrees>MD, PhD</degrees></personName><contactDetails><email>B.vandeWarrenburg@neuro.umcn.nl</email></contactDetails></creator><creator xml:id="au56" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Leonard H.</givenNames><familyName>van den Berg</familyName><degrees>MD, PhD</degrees></personName><contactDetails><email>l.h.vandenberg@umcutrecht.nl</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="NL" type="organization"><unparsedAffiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="NL" type="organization"><unparsedAffiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="IT" type="organization"><unparsedAffiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="SE" type="organization"><unparsedAffiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="DE" type="organization"><unparsedAffiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="NL" type="organization"><unparsedAffiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="NL" type="organization"><unparsedAffiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>Department of Pathology, Harvard Medical School, Boston, MA</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="US" type="organization"><unparsedAffiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</unparsedAffiliation></affiliation><affiliation xml:id="af12" countryCode="IT" type="organization"><unparsedAffiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af13" countryCode="BE" type="organization"><unparsedAffiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</unparsedAffiliation></affiliation><affiliation xml:id="af14" countryCode="BE" type="organization"><unparsedAffiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</unparsedAffiliation></affiliation><affiliation xml:id="af15" countryCode="BE" type="organization"><unparsedAffiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</unparsedAffiliation></affiliation><affiliation xml:id="af16" countryCode="ES" type="organization"><unparsedAffiliation>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain</unparsedAffiliation></affiliation><affiliation xml:id="af17" countryCode="DE" type="organization"><unparsedAffiliation>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af18" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurology, University of Ulm, Ulm, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af19" countryCode="DE" type="organization"><unparsedAffiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af20" countryCode="CH" type="organization"><unparsedAffiliation>Neuromuscular Diseases Unit, Kantonspital St Gallen, St Gallen, Switzerland</unparsedAffiliation></affiliation><affiliation xml:id="af21" countryCode="NL" type="organization"><unparsedAffiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af22" countryCode="NL" type="organization"><unparsedAffiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af23" countryCode="NL" type="organization"><unparsedAffiliation>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af24" countryCode="NL" type="organization"><unparsedAffiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af25" countryCode="NL" type="organization"><unparsedAffiliation>Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht, the Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="af26" countryCode="IT" type="organization"><unparsedAffiliation>Department of Neurology, University of Milan Medical School, “Dino Ferrari” Center, Milan, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af27" countryCode="US" type="organization"><unparsedAffiliation>University of California at Los Angeles Center for Neurobehavioral Genetics, Los Angeles, CA</unparsedAffiliation></affiliation><affiliation xml:id="af28" countryCode="US" type="organization"><unparsedAffiliation>Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA</unparsedAffiliation></affiliation><affiliation xml:id="af29" countryCode="US" type="organization"><unparsedAffiliation>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA</unparsedAffiliation></affiliation><affiliation xml:id="af30" countryCode="NL" type="organization"><unparsedAffiliation>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</unparsedAffiliation></affiliation></affiliationGroup><supportingInformation><p> Additional supporting information can be found in the online version of this article. </p><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana22611:ANG_Supplementary_Material_revised"></mediaResource><caption>Supp Info</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main">Objective:</title><p>Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (<i>ANG</i>) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying <i>ANG</i> variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether <i>ANG</i> variants could predispose to both ALS and PD.</p></section><section xml:id="abs1-2"><title type="main">Methods:</title><p>We reviewed all previous studies on <i>ANG</i> in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel‐Haenszel procedure was used to estimate odds ratios.</p></section><section xml:id="abs1-3"><title type="main">Results:</title><p>Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of <i>ANG</i> variants in both ALS and PD patients compared to control subjects (<i>p</i> = 9.3 × 10<sup>−6</sup> for ALS and <i>p</i> = 4.3 × 10<sup>−5</sup> for PD). The odds ratio for any <i>ANG</i> variant in patients versus controls was 9.2 for ALS and 6.7 for PD.</p></section><section xml:id="abs1-4"><title type="main">Interpretation:</title><p>The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and <i>ANG</i> variants. <i>ANG</i> is a genetic link between ALS and PD. ANN NEUROL 2011;70:964–973</p></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Angiogenin in PD and ALS</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis</title></titleInfo><name type="personal"><namePart type="given">Michael A.</namePart><namePart type="family">van Es</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Helenius J.</namePart><namePart type="family">Schelhaas</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul W. J.</namePart><namePart type="family">van Vught</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nicola</namePart><namePart type="family">Ticozzi</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation><affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter M.</namePart><namePart type="family">Andersen</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ewout J. N.</namePart><namePart type="family">Groen</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Claudia</namePart><namePart type="family">Schulte</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hylke M.</namePart><namePart type="family">Blauw</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Max</namePart><namePart type="family">Koppers</namePart><namePart type="termsOfAddress">MSc</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Frank P.</namePart><namePart type="family">Diekstra</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Katsumi</namePart><namePart type="family">Fumoto</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ashley Lyn</namePart><namePart type="family">LeClerc</namePart><namePart type="termsOfAddress">BA</namePart><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Pamela</namePart><namePart type="family">Keagle</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bastiaan R.</namePart><namePart type="family">Bloem</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hans</namePart><namePart type="family">Scheffer</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bart F. L.</namePart><namePart type="family">van Nuenen</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marka</namePart><namePart type="family">van Blitterswijk</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wouter</namePart><namePart type="family">van Rheenen</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anne‐Marie</namePart><namePart type="family">Wills</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick P.</namePart><namePart type="family">Lowe</namePart><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Guo‐fu</namePart><namePart type="family">Hu</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pathology, Harvard Medical School, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wenhao</namePart><namePart type="family">Yu</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hiroko</namePart><namePart type="family">Kishikawa</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pathology, Harvard Medical School, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="family">Wu</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rebecca D.</namePart><namePart type="family">Folkerth</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pathology, Brigham and Women's Hospital, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Claudio</namePart><namePart type="family">Mariani</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stefano</namePart><namePart type="family">Goldwurm</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gianni</namePart><namePart type="family">Pezzoli</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Philip</namePart><namePart type="family">Van Damme</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</affiliation><affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</affiliation><affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robin</namePart><namePart type="family">Lemmens</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</affiliation><affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</affiliation><affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Caroline</namePart><namePart type="family">Dahlberg</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anna</namePart><namePart type="family">Birve</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rubén</namePart><namePart type="family">Fernández‐Santiago</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>Department for Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain</affiliation><affiliation>Graduate School of Cellular and Molecular Neuroscience, International Max Planck Research School, Graduate Training Center of Neuroscience, Eberhard‐Karls University, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stefan</namePart><namePart type="family">Waibel</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Ulm, Ulm, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Klein</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Markus</namePart><namePart type="family">Weber</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Neuromuscular Diseases Unit, Kantonspital St Gallen, St Gallen, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anneke J.</namePart><namePart type="family">van der Kooi</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marianne</namePart><namePart type="family">de Visser</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Amsterdam Medical Center, Amsterdam, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dagmar</namePart><namePart type="family">Verbaan</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jacobus J.</namePart><namePart type="family">van Hilten</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Heutink</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eric A. M.</namePart><namePart type="family">Hennekam</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Edwin</namePart><namePart type="family">Cuppen</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Daniela</namePart><namePart type="family">Berg</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robert H.</namePart><namePart type="family">Brown Jr</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vincenzo</namePart><namePart type="family">Silani</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy</affiliation><affiliation>Department of Neurology, University of Milan Medical School, “Dino Ferrari” Center, Milan, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas</namePart><namePart type="family">Gasser</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center for Neurodegenerative Diseases, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Albert C.</namePart><namePart type="family">Ludolph</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, University of Ulm, Ulm, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wim</namePart><namePart type="family">Robberecht</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Experimental Neurology, University of Leuven, Leuven, Belgium</affiliation><affiliation>Vesalius Research Center, Flanders Institute for Biotechnology, Leuven, Belgium</affiliation><affiliation>Department of Neurology, University Hospital Leuven, University of Leuven, Leuven, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Roel A.</namePart><namePart type="family">Ophoff</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>University of California at Los Angeles Center for Neurobehavioral Genetics, Los Angeles, CA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan H.</namePart><namePart type="family">Veldink</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R. Jeroen</namePart><namePart type="family">Pasterkamp</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul I. W.</namePart><namePart type="family">de Bakker</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><affiliation>Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA</affiliation><affiliation>Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA</affiliation><affiliation>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John E.</namePart><namePart type="family">Landers</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, University of Massachusetts Medical School, Worcester, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bart P.</namePart><namePart type="family">van de Warrenburg</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Donders Instute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands</affiliation><affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Leonard H.</namePart><namePart type="family">van den Berg</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands</affiliation><affiliation>Bart P. van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Center for Neuroscience, Radboud University Nijmegen Medical Center, Geert Grooteplein‐Zuid 10, 6525 GA Nijmegen, the NetherlandsLeonard H. van den Berg, Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-12</dateIssued><dateCaptured encoding="w3cdtf">2011-05-21</dateCaptured><dateValid encoding="w3cdtf">2011-08-12</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="tables">3</extent><extent unit="references">50</extent><extent unit="words">6360</extent></physicalDescription><abstract lang="en">Objective:: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods:: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel‐Haenszel procedure was used to estimate odds ratios. Results:: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10−6 for ALS and p = 4.3 × 10−5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation:: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD. ANN NEUROL 2011;70:964–973</abstract><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><note type="content"> Additional supporting information can be found in the online version of this article.Supporting Info Item: Supp Info - </note><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>70</number></detail><detail type="issue"><caption>no.</caption><number>6</number></detail><extent unit="pages"><start>964</start><end>973</end><total>10</total></extent></part></relatedItem><identifier type="istex">1104402D2CD5B78610B101FB2326A7D93EC038A3</identifier><identifier type="DOI">10.1002/ana.22611</identifier><identifier type="ArticleID">ANA22611</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2011 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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