Genetic association between α‐synuclein and idiopathic parkinson's disease
Identifieur interne : 001425 ( Main/Corpus ); précédent : 001424; suivant : 001426Genetic association between α‐synuclein and idiopathic parkinson's disease
Auteurs : Denise M. Kay ; Stewart A. Factor ; Ali Samii ; Donald S. Higgins ; Alida Griffith ; John W. Roberts ; Berta C. Leis ; John G. Nutt ; Jennifer S. Montimurro ; Robert G. Keefe ; April J. Atkins ; Dora Yearout ; Cyrus P. Zabetian ; Haydeh PayamiSource :
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics [ 1552-4841 ] ; 2008-10-05.
English descriptors
Abstract
Point mutations and copy number variations in SNCA, the gene encoding α‐synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism (REP1) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency <0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR) = 0.86, P = 0.006 for 257‐carriers; OR = 1.25, P = 0.022 for 261‐carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, P = 0.002 in overall data, 0.003 in non‐familial PD, 0.001 in early‐onset PD; for 261, P = 0.056 in overall data, 0.024 in non‐familial PD, 0.052 in early‐onset PD). The 257‐associated risk was consistent with a dominant model [hazard ratio (HR) = 0.99, P = 0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR = 1.16, P = 0.004 for X/X vs. 257/X]. The 261‐associated risk was consistent with a recessive model (HR = 1.89, P = 0.026 for 261/261 vs. 261/X; HR = 0.95, P = 0.42 for X/X vs. 261/X). Genotype‐specific mean onset ages (±SD) ranged from 54.8 ± 12.1 for 261/261 to 59.4 ± 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (P = 0.055). Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. © 2008 Wiley‐Liss, Inc.
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DOI: 10.1002/ajmg.b.30758
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Kay</name><affiliation><mods:affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</mods:affiliation></affiliation></author><author><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A." last="Factor">Stewart A. Factor</name><affiliation><mods:affiliation>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, Georgia</mods:affiliation></affiliation></author><author><name sortKey="Samii, Ali" sort="Samii, Ali" uniqKey="Samii A" first="Ali" last="Samii">Ali Samii</name><affiliation><mods:affiliation>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Higgins, Donald S" sort="Higgins, Donald S" uniqKey="Higgins D" first="Donald S." last="Higgins">Donald S. Higgins</name><affiliation><mods:affiliation>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</mods:affiliation></affiliation></author><author><name sortKey="Griffith, Alida" sort="Griffith, Alida" uniqKey="Griffith A" first="Alida" last="Griffith">Alida Griffith</name><affiliation><mods:affiliation>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</mods:affiliation></affiliation></author><author><name sortKey="Roberts, John W" sort="Roberts, John W" uniqKey="Roberts J" first="John W." last="Roberts">John W. Roberts</name><affiliation><mods:affiliation>Virginia Mason Medical Center, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Leis, Berta C" sort="Leis, Berta C" uniqKey="Leis B" first="Berta C." last="Leis">Berta C. Leis</name><affiliation><mods:affiliation>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</mods:affiliation></affiliation></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G." last="Nutt">John G. Nutt</name><affiliation><mods:affiliation>Department of Neurology, Oregon Health and Science University, Portland, Oregon</mods:affiliation></affiliation></author><author><name sortKey="Montimurro, Jennifer S" sort="Montimurro, Jennifer S" uniqKey="Montimurro J" first="Jennifer S." last="Montimurro">Jennifer S. Montimurro</name><affiliation><mods:affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</mods:affiliation></affiliation></author><author><name sortKey="Keefe, Robert G" sort="Keefe, Robert G" uniqKey="Keefe R" first="Robert G." last="Keefe">Robert G. Keefe</name><affiliation><mods:affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</mods:affiliation></affiliation></author><author><name sortKey="Atkins, April J" sort="Atkins, April J" uniqKey="Atkins A" first="April J." last="Atkins">April J. Atkins</name><affiliation><mods:affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</mods:affiliation></affiliation></author><author><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><affiliation><mods:affiliation>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name><affiliation><mods:affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title level="j" type="abbrev">Am. J. Med. Genet.</title><idno type="ISSN">1552-4841</idno><idno type="eISSN">1552-485X</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2008-10-05">2008-10-05</date><biblScope unit="volume">147B</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="1222">1222</biblScope><biblScope unit="page" to="1230">1230</biblScope></imprint><idno type="ISSN">1552-4841</idno></series><idno type="istex">71249AF25E4410CF43277E6F33BF9D37CDB382E9</idno><idno type="DOI">10.1002/ajmg.b.30758</idno><idno type="ArticleID">AJMG30758</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1552-4841</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>REP1</term><term>age at onset</term><term>mode of inheritance</term><term>relative predispositional effects</term><term>risk</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Point mutations and copy number variations in SNCA, the gene encoding α‐synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism (REP1) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency <0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR) = 0.86, P = 0.006 for 257‐carriers; OR = 1.25, P = 0.022 for 261‐carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, P = 0.002 in overall data, 0.003 in non‐familial PD, 0.001 in early‐onset PD; for 261, P = 0.056 in overall data, 0.024 in non‐familial PD, 0.052 in early‐onset PD). The 257‐associated risk was consistent with a dominant model [hazard ratio (HR) = 0.99, P = 0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR = 1.16, P = 0.004 for X/X vs. 257/X]. The 261‐associated risk was consistent with a recessive model (HR = 1.89, P = 0.026 for 261/261 vs. 261/X; HR = 0.95, P = 0.42 for X/X vs. 261/X). Genotype‐specific mean onset ages (±SD) ranged from 54.8 ± 12.1 for 261/261 to 59.4 ± 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (P = 0.055). Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. © 2008 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Denise M. Kay</name><affiliations><json:string>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</json:string></affiliations></json:item><json:item><name>Stewart A. Factor</name><affiliations><json:string>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</json:string><json:string>Department of Neurology, Emory University School of Medicine, Atlanta, Georgia</json:string></affiliations></json:item><json:item><name>Ali Samii</name><affiliations><json:string>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Donald S. Higgins</name><affiliations><json:string>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</json:string></affiliations></json:item><json:item><name>Alida Griffith</name><affiliations><json:string>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</json:string></affiliations></json:item><json:item><name>John W. Roberts</name><affiliations><json:string>Virginia Mason Medical Center, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Berta C. Leis</name><affiliations><json:string>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</json:string></affiliations></json:item><json:item><name>John G. Nutt</name><affiliations><json:string>Department of Neurology, Oregon Health and Science University, Portland, Oregon</json:string></affiliations></json:item><json:item><name>Jennifer S. Montimurro</name><affiliations><json:string>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</json:string></affiliations></json:item><json:item><name>Robert G. Keefe</name><affiliations><json:string>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</json:string></affiliations></json:item><json:item><name>April J. Atkins</name><affiliations><json:string>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</json:string></affiliations></json:item><json:item><name>Dora Yearout</name><affiliations><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Cyrus P. Zabetian</name><affiliations><json:string>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Haydeh Payami</name><affiliations><json:string>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>REP1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>risk</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>age at onset</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>relative predispositional effects</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>mode of inheritance</value></json:item></subject><articleId><json:string>AJMG30758</json:string></articleId><language><json:string>eng</json:string></language><abstract>Point mutations and copy number variations in SNCA, the gene encoding α‐synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism (REP1) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency >0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR) = 0.86, P = 0.006 for 257‐carriers; OR = 1.25, P = 0.022 for 261‐carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, P = 0.002 in overall data, 0.003 in non‐familial PD, 0.001 in early‐onset PD; for 261, P = 0.056 in overall data, 0.024 in non‐familial PD, 0.052 in early‐onset PD). The 257‐associated risk was consistent with a dominant model [hazard ratio (HR) = 0.99, P = 0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR = 1.16, P = 0.004 for X/X vs. 257/X]. The 261‐associated risk was consistent with a recessive model (HR = 1.89, P = 0.026 for 261/261 vs. 261/X; HR = 0.95, P = 0.42 for X/X vs. 261/X). Genotype‐specific mean onset ages (±SD) ranged from 54.8 ± 12.1 for 261/261 to 59.4 ± 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (P = 0.055). Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. © 2008 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1709</abstractCharCount><pdfWordCount>5839</pdfWordCount><pdfCharCount>38128</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>252</abstractWordCount></qualityIndicators><title>Genetic association between α‐synuclein and idiopathic parkinson's disease</title><genre><json:string>article</json:string></genre><host><volume>147B</volume><publisherId><json:string>AJMG</json:string></publisherId><pages><total>9</total><last>1230</last><first>1222</first></pages><issn><json:string>1552-4841</json:string></issn><issue>7</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1552-485X</json:string></eissn><title>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><doi><json:string>10.1002/(ISSN)1552-485X</json:string></doi></host><publicationDate>2008</publicationDate><copyrightDate>2008</copyrightDate><doi><json:string>10.1002/ajmg.b.30758</json:string></doi><id>71249AF25E4410CF43277E6F33BF9D37CDB382E9</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/71249AF25E4410CF43277E6F33BF9D37CDB382E9/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/71249AF25E4410CF43277E6F33BF9D37CDB382E9/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/71249AF25E4410CF43277E6F33BF9D37CDB382E9/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Genetic association between α‐synuclein and idiopathic parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2008</date></publicationStmt><notesStmt><note type="content">*Please cite this article as follows: Kay DM, Factor SA, Samii A, Higgins DS, Griffith A, Roberts JW, Leis BC, Nutt JG, Montimurro JS, Keefe RG, Atkins AJ, Yearout D, Zabetian CP, Payami H. 2008. Genetic Association Between α‐Synuclein and Idiopathic Parkinson's Disease. Am J Med Genet Part B 147B:1222–1230.</note><note>Michael J. Fox Foundation Edmond J. Safra Global Genetics Consortia Grant</note><note>National Institutes of Health (NIH) National Institute for Neurological Disorders and Stroke grants - No. NS R01‐36960; No. K08‐NS044138;</note><note>VA Merit Award</note><note>NIH National Institutes of Aging grant - No. AG 08017;</note><note>Mental Health and Geriatric Research Education and Clinical Centers at the VA Puget Sound Health Care System</note><note>Genomics Institute of the New York State Department of Health Wadsworth Center</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Genetic association between α‐synuclein and idiopathic parkinson's disease</title><author><persName><forename type="first">Denise M.</forename><surname>Kay</surname></persName><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation></author><author><persName><forename type="first">Stewart A.</forename><surname>Factor</surname></persName><affiliation>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</affiliation><affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, Georgia</affiliation></author><author><persName><forename type="first">Ali</forename><surname>Samii</surname></persName><affiliation>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation></author><author><persName><forename type="first">Donald S.</forename><surname>Higgins</surname></persName><affiliation>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</affiliation></author><author><persName><forename type="first">Alida</forename><surname>Griffith</surname></persName><affiliation>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</affiliation></author><author><persName><forename type="first">John W.</forename><surname>Roberts</surname></persName><affiliation>Virginia Mason Medical Center, Seattle, Washington</affiliation></author><author><persName><forename type="first">Berta C.</forename><surname>Leis</surname></persName><affiliation>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</affiliation></author><author><persName><forename type="first">John G.</forename><surname>Nutt</surname></persName><affiliation>Department of Neurology, Oregon Health and Science University, Portland, Oregon</affiliation></author><author><persName><forename type="first">Jennifer S.</forename><surname>Montimurro</surname></persName><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation></author><author><persName><forename type="first">Robert G.</forename><surname>Keefe</surname></persName><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation></author><author><persName><forename type="first">April J.</forename><surname>Atkins</surname></persName><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation></author><author><persName><forename type="first">Dora</forename><surname>Yearout</surname></persName><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation></author><author><persName><forename type="first">Cyrus P.</forename><surname>Zabetian</surname></persName><affiliation>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation></author><author><persName><forename type="first">Haydeh</forename><surname>Payami</surname></persName><note type="correspondence"><p>Correspondence: New York State Department of Health, Wadsworth Center, PO Box 22002 Albany, NY 12208.</p></note><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation></author></analytic><monogr><title level="j">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title level="j" type="abbrev">Am. J. Med. Genet.</title><idno type="pISSN">1552-4841</idno><idno type="eISSN">1552-485X</idno><idno type="DOI">10.1002/(ISSN)1552-485X</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2008-10-05"></date><biblScope unit="volume">147B</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="1222">1222</biblScope><biblScope unit="page" to="1230">1230</biblScope></imprint></monogr><idno type="istex">71249AF25E4410CF43277E6F33BF9D37CDB382E9</idno><idno type="DOI">10.1002/ajmg.b.30758</idno><idno type="ArticleID">AJMG30758</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2008</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Point mutations and copy number variations in SNCA, the gene encoding α‐synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism (REP1) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency <0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR) = 0.86, P = 0.006 for 257‐carriers; OR = 1.25, P = 0.022 for 261‐carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, P = 0.002 in overall data, 0.003 in non‐familial PD, 0.001 in early‐onset PD; for 261, P = 0.056 in overall data, 0.024 in non‐familial PD, 0.052 in early‐onset PD). The 257‐associated risk was consistent with a dominant model [hazard ratio (HR) = 0.99, P = 0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR = 1.16, P = 0.004 for X/X vs. 257/X]. The 261‐associated risk was consistent with a recessive model (HR = 1.89, P = 0.026 for 261/261 vs. 261/X; HR = 0.95, P = 0.42 for X/X vs. 261/X). Genotype‐specific mean onset ages (±SD) ranged from 54.8 ± 12.1 for 261/261 to 59.4 ± 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (P = 0.055). Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. © 2008 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>REP1</term></item><item><term>risk</term></item><item><term>age at onset</term></item><item><term>relative predispositional effects</term></item><item><term>mode of inheritance</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2007-12-11">Received</change><change when="2008-03-03">Registration</change><change when="2008-10-05">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/71249AF25E4410CF43277E6F33BF9D37CDB382E9/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)1552-485X</doi><issn type="print">1552-4841</issn><issn type="electronic">1552-485X</issn><idGroup><id type="product" value="AJMG"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="AMERICAN JOURNAL OF MEDICAL GENETICS PART B: NEUROPSYCHIATRIC GENETICS">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title type="short">Am. 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#af3"><personName><givenNames>Stewart A.</givenNames><familyName>Factor</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af4 #af5"><personName><givenNames>Ali</givenNames><familyName>Samii</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Donald S.</givenNames><familyName>Higgins</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Alida</givenNames><familyName>Griffith</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af7"><personName><givenNames>John W.</givenNames><familyName>Roberts</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Berta C.</givenNames><familyName>Leis</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af8"><personName><givenNames>John G.</givenNames><familyName>Nutt</familyName></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Jennifer S.</givenNames><familyName>Montimurro</familyName></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Robert G.</givenNames><familyName>Keefe</familyName></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af1"><personName><givenNames>April J.</givenNames><familyName>Atkins</familyName></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af5 #af9"><personName><givenNames>Dora</givenNames><familyName>Yearout</familyName></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af4 #af5 #af9"><personName><givenNames>Cyrus P.</givenNames><familyName>Zabetian</familyName></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Haydeh</givenNames><familyName>Payami</familyName></personName><contactDetails><email>hpayami@wadsworth.org</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Emory University School of Medicine, Atlanta, Georgia</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="US" type="organization"><unparsedAffiliation>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="US" type="organization"><unparsedAffiliation>Virginia Mason Medical Center, Seattle, Washington</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Oregon Health and Science University, Portland, Oregon</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="US" type="organization"><unparsedAffiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">REP1</keyword><keyword xml:id="kwd2">risk</keyword><keyword xml:id="kwd3">age at onset</keyword><keyword xml:id="kwd4">relative predispositional effects</keyword><keyword xml:id="kwd5">mode of inheritance</keyword></keywordGroup><fundingInfo><fundingAgency>Michael J. Fox Foundation Edmond J. Safra Global Genetics Consortia Grant</fundingAgency></fundingInfo><fundingInfo><fundingAgency>National Institutes of Health (NIH) National Institute for Neurological Disorders and Stroke grants</fundingAgency><fundingNumber>NS R01‐36960</fundingNumber><fundingNumber>K08‐NS044138</fundingNumber></fundingInfo><fundingInfo><fundingAgency>VA Merit Award</fundingAgency></fundingInfo><fundingInfo><fundingAgency>NIH National Institutes of Aging grant</fundingAgency><fundingNumber>AG 08017</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Mental Health and Geriatric Research Education and Clinical Centers at the VA Puget Sound Health Care System</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Genomics Institute of the New York State Department of Health Wadsworth Center</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Point mutations and copy number variations in <i>SNCA</i>, the gene encoding α‐synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism (REP1) in the <i>SNCA</i> promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency <0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR) = 0.86, <i>P</i> = 0.006 for 257‐carriers; OR = 1.25, <i>P</i> = 0.022 for 261‐carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, <i>P</i> = 0.002 in overall data, 0.003 in non‐familial PD, 0.001 in early‐onset PD; for 261, <i>P</i> = 0.056 in overall data, 0.024 in non‐familial PD, 0.052 in early‐onset PD). The 257‐associated risk was consistent with a dominant model [hazard ratio (HR) = 0.99, <i>P</i> = 0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR = 1.16, <i>P</i> = 0.004 for X/X vs. 257/X]. The 261‐associated risk was consistent with a recessive model (HR = 1.89, <i>P</i> = 0.026 for 261/261 vs. 261/X; HR = 0.95, <i>P</i> = 0.42 for X/X vs. 261/X). Genotype‐specific mean onset ages (±SD) ranged from 54.8 ± 12.1 for 261/261 to 59.4 ± 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (<i>P</i> = 0.055). Genetic variation in <i>SNCA</i> and its regulatory regions play an important role in both familial and sporadic PD. © 2008 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Please cite this article as follows: Kay DM, Factor SA, Samii A, Higgins DS, Griffith A, Roberts JW, Leis BC, Nutt JG, Montimurro JS, Keefe RG, Atkins AJ, Yearout D, Zabetian CP, Payami H. 2008. Genetic Association Between α‐Synuclein and Idiopathic Parkinson's Disease. Am J Med Genet Part B 147B:1222–1230.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Genetic association between α‐synuclein and idiopathic parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>α‐Synuclein REP1 & PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Genetic association between α‐synuclein and idiopathic parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Denise M.</namePart><namePart type="family">Kay</namePart><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stewart A.</namePart><namePart type="family">Factor</namePart><affiliation>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</affiliation><affiliation>Department of Neurology, Emory University School of Medicine, Atlanta, Georgia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ali</namePart><namePart type="family">Samii</namePart><affiliation>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Donald S.</namePart><namePart type="family">Higgins</namePart><affiliation>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alida</namePart><namePart type="family">Griffith</namePart><affiliation>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John W.</namePart><namePart type="family">Roberts</namePart><affiliation>Virginia Mason Medical Center, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Berta C.</namePart><namePart type="family">Leis</namePart><affiliation>Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John G.</namePart><namePart type="family">Nutt</namePart><affiliation>Department of Neurology, Oregon Health and Science University, Portland, Oregon</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jennifer S.</namePart><namePart type="family">Montimurro</namePart><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robert G.</namePart><namePart type="family">Keefe</namePart><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">April J.</namePart><namePart type="family">Atkins</namePart><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dora</namePart><namePart type="family">Yearout</namePart><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cyrus P.</namePart><namePart type="family">Zabetian</namePart><affiliation>Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Haydeh</namePart><namePart type="family">Payami</namePart><affiliation>Division of Genetic Disorders, Wadsworth Center, New York State Department of Health, Albany, New York</affiliation><description>Correspondence: New York State Department of Health, Wadsworth Center, PO Box 22002 Albany, NY 12208.</description><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">2008-10-05</dateIssued><dateCaptured encoding="w3cdtf">2007-12-11</dateCaptured><dateValid encoding="w3cdtf">2008-03-03</dateValid><copyrightDate encoding="w3cdtf">2008</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="figures">2</extent><extent unit="tables">5</extent><extent unit="references">26</extent><extent unit="words">8422</extent></physicalDescription><abstract lang="en">Point mutations and copy number variations in SNCA, the gene encoding α‐synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism (REP1) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency <0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR) = 0.86, P = 0.006 for 257‐carriers; OR = 1.25, P = 0.022 for 261‐carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, P = 0.002 in overall data, 0.003 in non‐familial PD, 0.001 in early‐onset PD; for 261, P = 0.056 in overall data, 0.024 in non‐familial PD, 0.052 in early‐onset PD). The 257‐associated risk was consistent with a dominant model [hazard ratio (HR) = 0.99, P = 0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR = 1.16, P = 0.004 for X/X vs. 257/X]. The 261‐associated risk was consistent with a recessive model (HR = 1.89, P = 0.026 for 261/261 vs. 261/X; HR = 0.95, P = 0.42 for X/X vs. 261/X). Genotype‐specific mean onset ages (±SD) ranged from 54.8 ± 12.1 for 261/261 to 59.4 ± 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (P = 0.055). Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. © 2008 Wiley‐Liss, Inc.</abstract><note type="content">*Please cite this article as follows: Kay DM, Factor SA, Samii A, Higgins DS, Griffith A, Roberts JW, Leis BC, Nutt JG, Montimurro JS, Keefe RG, Atkins AJ, Yearout D, Zabetian CP, Payami H. 2008. Genetic Association Between α‐Synuclein and Idiopathic Parkinson's Disease. Am J Med Genet Part B 147B:1222–1230.</note><note type="funding">Michael J. Fox Foundation Edmond J. Safra Global Genetics Consortia Grant</note><note type="funding">National Institutes of Health (NIH) National Institute for Neurological Disorders and Stroke grants - No. NS R01‐36960; No. K08‐NS044138; </note><note type="funding">VA Merit Award</note><note type="funding">NIH National Institutes of Aging grant - No. AG 08017; </note><note type="funding">Mental Health and Geriatric Research Education and Clinical Centers at the VA Puget Sound Health Care System</note><note type="funding">Genomics Institute of the New York State Department of Health Wadsworth Center</note><subject lang="en"><genre>Keywords</genre><topic>REP1</topic><topic>risk</topic><topic>age at onset</topic><topic>relative predispositional effects</topic><topic>mode of inheritance</topic></subject><relatedItem type="host"><titleInfo><title>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title></titleInfo><titleInfo type="abbreviated"><title>Am. J. Med. Genet.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">1552-4841</identifier><identifier type="eISSN">1552-485X</identifier><identifier type="DOI">10.1002/(ISSN)1552-485X</identifier><identifier type="PublisherID">AJMG</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>147B</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>1222</start><end>1230</end><total>9</total></extent></part></relatedItem><relatedItem type="preceding"><titleInfo><title>American Journal of Medical Genetics</title></titleInfo><identifier type="ISSN">0148-7299</identifier><identifier type="ISSN">1096-8628</identifier><part><date point="end">2004</date></part></relatedItem><identifier type="istex">71249AF25E4410CF43277E6F33BF9D37CDB382E9</identifier><identifier type="DOI">10.1002/ajmg.b.30758</identifier><identifier type="ArticleID">AJMG30758</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2008 Wiley‐Liss, Inc.</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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