Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease
Identifieur interne : 000336 ( Ncbi/Curation ); précédent : 000335; suivant : 000337Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease
Auteurs : Chuong Do [États-Unis] ; Joyce Tung [États-Unis] ; Elizabeth Dorfman [États-Unis] ; Amy Kiefer [États-Unis] ; Emily Drabant [États-Unis] ; Uta Francke [États-Unis] ; Joanna Mountain [États-Unis] ; Samuel Goldman [États-Unis] ; Caroline Tanner [États-Unis] ; J Langston [États-Unis] ; Anne Wojcicki [États-Unis] ; Nicholas Eriksson [États-Unis]Source :
- PLoS Genetics [ 1553-7390 ] ; 2011.
Abstract
Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD–rs6812193 near
Url:
DOI: 10.1371/journal.pgen.1002141
PubMed: 21738487
PubMed Central: 3121750
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xml:lang="en"><p>Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD–rs6812193 near <italic>SCARB2</italic> (<inline-formula><inline-graphic xlink:href="pgen.1002141.e001.jpg" mimetype="image"></inline-graphic></inline-formula>, <inline-formula><inline-graphic xlink:href="pgen.1002141.e002.jpg" mimetype="image"></inline-graphic></inline-formula>) and rs11868035 near <italic>SREBF1</italic>/<italic>RAI1</italic> (<inline-formula><inline-graphic xlink:href="pgen.1002141.e003.jpg" mimetype="image"></inline-graphic></inline-formula>, <inline-formula><inline-graphic xlink:href="pgen.1002141.e004.jpg" mimetype="image"></inline-graphic></inline-formula>)—both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including <italic>LRRK2</italic>, <italic>GBA</italic>, <italic>SNCA</italic>, <italic>MAPT</italic>, <italic>GAK</italic>, and the <italic>HLA</italic> region), providing support for our novel study design. Relying on a recently proposed method based on genome-wide sharing estimates between distantly related individuals, we estimated the heritability of PD to be at least 0.27. Finally, using sparse regression techniques, we constructed predictive models that account for 6%–7% of the total variance in liability and that suggest the presence of true associations just beyond genome-wide significance, as confirmed through both internal and external cross-validation. These results indicate a substantial, but by no means total, contribution of genetics underlying susceptibility to both early-onset and late-onset PD, suggesting that, despite the novel associations discovered here and elsewhere, the majority of the genetic component for Parkinson's disease remains to be discovered.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Polymeropoulos, Mh" uniqKey="Polymeropoulos M">MH Polymeropoulos</name></author><author><name sortKey="Lavedan, C" uniqKey="Lavedan C">C Lavedan</name></author><author><name sortKey="Leroy, E" uniqKey="Leroy E">E Leroy</name></author><author><name sortKey="Ide, Se" uniqKey="Ide S">SE Ide</name></author><author><name sortKey="Dehejia, A" uniqKey="Dehejia A">A Dehejia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Singleton, Ab" uniqKey="Singleton A">AB Singleton</name></author><author><name sortKey="Farrer, M" uniqKey="Farrer M">M 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HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Curation/RBID.i -Sk "pubmed:21738487" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Curation/biblio.hfd \
| NlmPubMed2Wicri -a JankovicV1
| This area was generated with Dilib version V0.6.19. |  |