No Genetic Overlap Between Circulating Iron Levels and Alzheimer's Disease.
Identifieur interne : 001295 ( PubMed/Corpus ); précédent : 001294; suivant : 001296No Genetic Overlap Between Circulating Iron Levels and Alzheimer's Disease.
Auteurs : Michelle K. Lupton ; Beben Benyamin ; Petroula Proitsi ; Dale R. Nyholt ; Manuel A. Ferreira ; Grant W. Montgomery ; Andrew C. Heath ; Pamela A. Madden ; Sarah E. Medland ; Scott D. Gordon ; Simon Lovestone ; Magda Tsolaki ; Iwona Kloszewska ; Hilkka Soininen ; Patrizia Mecocci ; Bruno Vellas ; John F. Powell ; Ashley I. Bush ; Margaret J. Wright ; Nicholas G. Martin ; John B. WhitfieldSource :
- Journal of Alzheimer's disease : JAD [ 1875-8908 ] ; 2017.
Abstract
Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.
DOI: 10.3233/JAD-170027
PubMed: 28582860
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pubmed:28582860Le document en format XML
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<author><name sortKey="Lovestone, Simon" sort="Lovestone, Simon" uniqKey="Lovestone S" first="Simon" last="Lovestone">Simon Lovestone</name>
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<author><name sortKey="Tsolaki, Magda" sort="Tsolaki, Magda" uniqKey="Tsolaki M" first="Magda" last="Tsolaki">Magda Tsolaki</name>
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<author><name sortKey="Kloszewska, Iwona" sort="Kloszewska, Iwona" uniqKey="Kloszewska I" first="Iwona" last="Kloszewska">Iwona Kloszewska</name>
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<author><name sortKey="Mecocci, Patrizia" sort="Mecocci, Patrizia" uniqKey="Mecocci P" first="Patrizia" last="Mecocci">Patrizia Mecocci</name>
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<author><name sortKey="Bush, Ashley I" sort="Bush, Ashley I" uniqKey="Bush A" first="Ashley I" last="Bush">Ashley I. Bush</name>
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<author><name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J" last="Wright">Margaret J. Wright</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">No Genetic Overlap Between Circulating Iron Levels and Alzheimer's Disease.</title>
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<author><name sortKey="Proitsi, Petroula" sort="Proitsi, Petroula" uniqKey="Proitsi P" first="Petroula" last="Proitsi">Petroula Proitsi</name>
<affiliation><nlm:affiliation>Institute of Psychiatry Psychology and Neuroscience, Kings College London, UK.</nlm:affiliation>
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<author><name sortKey="Nyholt, Dale R" sort="Nyholt, Dale R" uniqKey="Nyholt D" first="Dale R" last="Nyholt">Dale R. Nyholt</name>
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<author><name sortKey="Ferreira, Manuel A" sort="Ferreira, Manuel A" uniqKey="Ferreira M" first="Manuel A" last="Ferreira">Manuel A. Ferreira</name>
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<author><name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W" last="Montgomery">Grant W. Montgomery</name>
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<author><name sortKey="Heath, Andrew C" sort="Heath, Andrew C" uniqKey="Heath A" first="Andrew C" last="Heath">Andrew C. Heath</name>
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<author><name sortKey="Madden, Pamela A" sort="Madden, Pamela A" uniqKey="Madden P" first="Pamela A" last="Madden">Pamela A. Madden</name>
<affiliation><nlm:affiliation>Washington University School of Medicine, StLouis, MO, USA.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Medland, Sarah E" sort="Medland, Sarah E" uniqKey="Medland S" first="Sarah E" last="Medland">Sarah E. Medland</name>
<affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</nlm:affiliation>
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<author><name sortKey="Gordon, Scott D" sort="Gordon, Scott D" uniqKey="Gordon S" first="Scott D" last="Gordon">Scott D. Gordon</name>
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<author><name sortKey="Lovestone, Simon" sort="Lovestone, Simon" uniqKey="Lovestone S" first="Simon" last="Lovestone">Simon Lovestone</name>
<affiliation><nlm:affiliation>Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.</nlm:affiliation>
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<author><name sortKey="Tsolaki, Magda" sort="Tsolaki, Magda" uniqKey="Tsolaki M" first="Magda" last="Tsolaki">Magda Tsolaki</name>
<affiliation><nlm:affiliation>Memory and Dementia Centre, 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kloszewska, Iwona" sort="Kloszewska, Iwona" uniqKey="Kloszewska I" first="Iwona" last="Kloszewska">Iwona Kloszewska</name>
<affiliation><nlm:affiliation>Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Soininen, Hilkka" sort="Soininen, Hilkka" uniqKey="Soininen H" first="Hilkka" last="Soininen">Hilkka Soininen</name>
<affiliation><nlm:affiliation>Department of Neurology, University of EasternFinland and Kuopio University Hospital, Kuopio, Finland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mecocci, Patrizia" sort="Mecocci, Patrizia" uniqKey="Mecocci P" first="Patrizia" last="Mecocci">Patrizia Mecocci</name>
<affiliation><nlm:affiliation>Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Vellas, Bruno" sort="Vellas, Bruno" uniqKey="Vellas B" first="Bruno" last="Vellas">Bruno Vellas</name>
<affiliation><nlm:affiliation>Gerontopole, CHU, UMR INSERM 1027, University ofToulouse, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Powell, John F" sort="Powell, John F" uniqKey="Powell J" first="John F" last="Powell">John F. Powell</name>
<affiliation><nlm:affiliation>Institute of Psychiatry Psychology and Neuroscience, Kings College London, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bush, Ashley I" sort="Bush, Ashley I" uniqKey="Bush A" first="Ashley I" last="Bush">Ashley I. Bush</name>
<affiliation><nlm:affiliation>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J" last="Wright">Margaret J. Wright</name>
<affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name>
<affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Whitfield, John B" sort="Whitfield, John B" uniqKey="Whitfield J" first="John B" last="Whitfield">John B. Whitfield</name>
<affiliation><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</nlm:affiliation>
</affiliation>
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<series><title level="j">Journal of Alzheimer's disease : JAD</title>
<idno type="eISSN">1875-8908</idno>
<imprint><date when="2017" type="published">2017</date>
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<front><div type="abstract" xml:lang="en">Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.</div>
</front>
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<Title>Journal of Alzheimer's disease : JAD</Title>
<ISOAbbreviation>J. Alzheimers Dis.</ISOAbbreviation>
</Journal>
<ArticleTitle>No Genetic Overlap Between Circulating Iron Levels and Alzheimer's Disease.</ArticleTitle>
<Pagination><MedlinePgn>85-99</MedlinePgn>
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<Abstract><AbstractText>Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lupton</LastName>
<ForeName>Michelle K</ForeName>
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</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Benyamin</LastName>
<ForeName>Beben</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Queensland Brain Institute, University of Queensland, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Proitsi</LastName>
<ForeName>Petroula</ForeName>
<Initials>P</Initials>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nyholt</LastName>
<ForeName>Dale R</ForeName>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ferreira</LastName>
<ForeName>Manuel A</ForeName>
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</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Montgomery</LastName>
<ForeName>Grant W</ForeName>
<Initials>GW</Initials>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Heath</LastName>
<ForeName>Andrew C</ForeName>
<Initials>AC</Initials>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Madden</LastName>
<ForeName>Pamela A</ForeName>
<Initials>PA</Initials>
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</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Medland</LastName>
<ForeName>Sarah E</ForeName>
<Initials>SE</Initials>
<AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gordon</LastName>
<ForeName>Scott D</ForeName>
<Initials>SD</Initials>
<AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>GERAD1 Consortium</CollectiveName>
</Author>
<Author ValidYN="Y"><CollectiveName>Alzheimer’s Disease Neuroimaging Initiative</CollectiveName>
</Author>
<Author ValidYN="Y"><LastName>Lovestone</LastName>
<ForeName>Simon</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tsolaki</LastName>
<ForeName>Magda</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Memory and Dementia Centre, 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kloszewska</LastName>
<ForeName>Iwona</ForeName>
<Initials>I</Initials>
<AffiliationInfo><Affiliation>Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Soininen</LastName>
<ForeName>Hilkka</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, University of EasternFinland and Kuopio University Hospital, Kuopio, Finland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mecocci</LastName>
<ForeName>Patrizia</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Vellas</LastName>
<ForeName>Bruno</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Gerontopole, CHU, UMR INSERM 1027, University ofToulouse, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Powell</LastName>
<ForeName>John F</ForeName>
<Initials>JF</Initials>
<AffiliationInfo><Affiliation>Institute of Psychiatry Psychology and Neuroscience, Kings College London, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bush</LastName>
<ForeName>Ashley I</ForeName>
<Initials>AI</Initials>
<AffiliationInfo><Affiliation>Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wright</LastName>
<ForeName>Margaret J</ForeName>
<Initials>MJ</Initials>
<AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Queensland Brain Institute, University of Queensland, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Centre for Advanced Imaging, University of Queensland, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Martin</LastName>
<ForeName>Nicholas G</ForeName>
<Initials>NG</Initials>
<AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Whitfield</LastName>
<ForeName>John B</ForeName>
<Initials>JB</Initials>
<AffiliationInfo><Affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Australia.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
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<MedlineJournalInfo><Country>Netherlands</Country>
<MedlineTA>J Alzheimers Dis</MedlineTA>
<NlmUniqueID>9814863</NlmUniqueID>
<ISSNLinking>1387-2877</ISSNLinking>
</MedlineJournalInfo>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Alzheimer’s disease</Keyword>
<Keyword MajorTopicYN="N">apolipoproteins E</Keyword>
<Keyword MajorTopicYN="N">dementia</Keyword>
<Keyword MajorTopicYN="N">ferritin</Keyword>
<Keyword MajorTopicYN="N">genetic profile scores</Keyword>
<Keyword MajorTopicYN="N">genome-wide association study</Keyword>
<Keyword MajorTopicYN="N">iron</Keyword>
<Keyword MajorTopicYN="N">population genetics</Keyword>
<Keyword MajorTopicYN="N">transferrin</Keyword>
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