Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease
Identifieur interne : 000271 ( Ncbi/Curation ); précédent : 000270; suivant : 000272Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease
Auteurs : Todd Edwards ; William Scott ; Cherylyn Almonte ; Amber Burt ; Eric Powell ; Gary Beecham ; Liyong Wang ; Stephan Züchner ; Ioanna Konidari ; Gaofeng Wang ; Carlos Singer ; Fatta Nahab ; Burton Scott ; Jeffrey Stajich ; Margaret Pericak ; Jonathan Haines ; Jeffery Vance ; Eden MartinSource :
- Annals of human genetics [ 0003-4800 ] ; 2010.
Abstract
Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies have also implicated several genes as PD risk loci with strong, but not genome-wide significant, associations.
In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in
Url:
DOI: 10.1111/j.1469-1809.2009.00560.x
PubMed: 20070850
PubMed Central: 2853717
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Todd Edwards<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Neurology, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A3">Department of Neurology, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Medicine, Duke University Medical Center, Duke University</nlm:aff>
<wicri:noCountry code="subfield">Duke University</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Medicine, Duke University Medical Center, Duke University</nlm:aff>
<wicri:noCountry code="subfield">Duke University</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A2">Center for Human Genetics Research, Vanderbilt University Medical Center, Vanderbilt University</nlm:aff>
<wicri:noCountry code="subfield">Vanderbilt University</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
Le document en format XML
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<author><name sortKey="Powell, Eric H" sort="Powell, Eric H" uniqKey="Powell E" first="Eric" last="Powell">Eric Powell</name>
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<author><name sortKey="Wang, Liyong" sort="Wang, Liyong" uniqKey="Wang L" first="Liyong" last="Wang">Liyong Wang</name>
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<author><name sortKey="Zuchner, Stephan" sort="Zuchner, Stephan" uniqKey="Zuchner S" first="Stephan" last="Züchner">Stephan Züchner</name>
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<author><name sortKey="Konidari, Ioanna" sort="Konidari, Ioanna" uniqKey="Konidari I" first="Ioanna" last="Konidari">Ioanna Konidari</name>
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<author><name sortKey="Wang, Gaofeng" sort="Wang, Gaofeng" uniqKey="Wang G" first="Gaofeng" last="Wang">Gaofeng Wang</name>
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<author><name sortKey="Singer, Carlos" sort="Singer, Carlos" uniqKey="Singer C" first="Carlos" last="Singer">Carlos Singer</name>
<affiliation><nlm:aff id="A3">Department of Neurology, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
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<author><name sortKey="Nahab, Fatta" sort="Nahab, Fatta" uniqKey="Nahab F" first="Fatta" last="Nahab">Fatta Nahab</name>
<affiliation><nlm:aff id="A3">Department of Neurology, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
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<author><name sortKey="Scott, Burton" sort="Scott, Burton" uniqKey="Scott B" first="Burton" last="Scott">Burton Scott</name>
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<wicri:noCountry code="subfield">Duke University</wicri:noCountry>
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<author><name sortKey="Stajich, Jeffrey M" sort="Stajich, Jeffrey M" uniqKey="Stajich J" first="Jeffrey" last="Stajich">Jeffrey Stajich</name>
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<wicri:noCountry code="subfield">Duke University</wicri:noCountry>
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<author><name sortKey="Pericak Vance, Margaret" sort="Pericak Vance, Margaret" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
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<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Haines, Jonathan" sort="Haines, Jonathan" uniqKey="Haines J" first="Jonathan" last="Haines">Jonathan Haines</name>
<affiliation><nlm:aff id="A2">Center for Human Genetics Research, Vanderbilt University Medical Center, Vanderbilt University</nlm:aff>
<wicri:noCountry code="subfield">Vanderbilt University</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide association study confirms SNPs in <italic>SNCA</italic>
and the <italic>MAPT</italic>
region as common risk factors for Parkinson disease</title>
<author><name sortKey="Edwards, Todd L" sort="Edwards, Todd L" uniqKey="Edwards T" first="Todd" last="Edwards">Todd Edwards</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Scott, William K" sort="Scott, William K" uniqKey="Scott W" first="William" last="Scott">William Scott</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Almonte, Cherylyn" sort="Almonte, Cherylyn" uniqKey="Almonte C" first="Cherylyn" last="Almonte">Cherylyn Almonte</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Burt, Amber" sort="Burt, Amber" uniqKey="Burt A" first="Amber" last="Burt">Amber Burt</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Powell, Eric H" sort="Powell, Eric H" uniqKey="Powell E" first="Eric" last="Powell">Eric Powell</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Beecham, Gary W" sort="Beecham, Gary W" uniqKey="Beecham G" first="Gary" last="Beecham">Gary Beecham</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Wang, Liyong" sort="Wang, Liyong" uniqKey="Wang L" first="Liyong" last="Wang">Liyong Wang</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Zuchner, Stephan" sort="Zuchner, Stephan" uniqKey="Zuchner S" first="Stephan" last="Züchner">Stephan Züchner</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Konidari, Ioanna" sort="Konidari, Ioanna" uniqKey="Konidari I" first="Ioanna" last="Konidari">Ioanna Konidari</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Wang, Gaofeng" sort="Wang, Gaofeng" uniqKey="Wang G" first="Gaofeng" last="Wang">Gaofeng Wang</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Singer, Carlos" sort="Singer, Carlos" uniqKey="Singer C" first="Carlos" last="Singer">Carlos Singer</name>
<affiliation><nlm:aff id="A3">Department of Neurology, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Nahab, Fatta" sort="Nahab, Fatta" uniqKey="Nahab F" first="Fatta" last="Nahab">Fatta Nahab</name>
<affiliation><nlm:aff id="A3">Department of Neurology, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Scott, Burton" sort="Scott, Burton" uniqKey="Scott B" first="Burton" last="Scott">Burton Scott</name>
<affiliation><nlm:aff id="A4">Department of Medicine, Duke University Medical Center, Duke University</nlm:aff>
<wicri:noCountry code="subfield">Duke University</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Stajich, Jeffrey M" sort="Stajich, Jeffrey M" uniqKey="Stajich J" first="Jeffrey" last="Stajich">Jeffrey Stajich</name>
<affiliation><nlm:aff id="A4">Department of Medicine, Duke University Medical Center, Duke University</nlm:aff>
<wicri:noCountry code="subfield">Duke University</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Pericak Vance, Margaret" sort="Pericak Vance, Margaret" uniqKey="Pericak Vance M" first="Margaret" last="Pericak">Margaret Pericak</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Haines, Jonathan" sort="Haines, Jonathan" uniqKey="Haines J" first="Jonathan" last="Haines">Jonathan Haines</name>
<affiliation><nlm:aff id="A2">Center for Human Genetics Research, Vanderbilt University Medical Center, Vanderbilt University</nlm:aff>
<wicri:noCountry code="subfield">Vanderbilt University</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Vance, Jeffery M" sort="Vance, Jeffery M" uniqKey="Vance J" first="Jeffery" last="Vance">Jeffery Vance</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden" last="Martin">Eden Martin</name>
<affiliation><nlm:aff id="A1">John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami</nlm:aff>
<wicri:noCountry code="subfield">University of Miami</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">Annals of human genetics</title>
<idno type="ISSN">0003-4800</idno>
<idno type="e-ISSN">1469-1809</idno>
<imprint><date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
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<front><div type="abstract" xml:lang="en"><title>SUMMARY</title>
<p id="P1">Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies have also implicated several genes as PD risk loci with strong, but not genome-wide significant, associations.</p>
<p id="P2">In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in <italic>SNCA</italic>
(rs2736990, p-value = 6.7×10<sup>−8</sup>
; genome-wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17–1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the <italic>MAPT</italic>
region (rs11012, p-value = 5.6×10<sup>−8</sup>
; genome-wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62–0.79] T vs. C allele, PAR% = 8%) were genome-wide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that <italic>SNCA</italic>
and the <italic>MAPT</italic>
region are major genes whose common variants are influencing risk of PD.</p>
</div>
</front>
</TEI>
</record>
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