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PMID: 21738487 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease.

PLoS genetics ·Vol. 7 ·No. 6 ·2011-06-00 ·Pages e1002141

Do CB, Tung JY, Dorfman E, Kiefer AK, Drabant EM, Francke U, Mountain JL, Goldman SM, Tanner CM, Langston JW, Wojcicki A, Eriksson N

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 SCARB2 (p = 7.6 × 10(-10), OR = 0.84) and rs11868035 near SREBF1/RAI1 (p = 5.6 × 10(-8), OR = 0.85)-both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA 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.

MeSH Terms
Databases, Factual Genetic Loci/genetics Genetic Predisposition to Disease Genome-Wide Association Study Heredity/genetics Humans Internet Parkinson Disease/genetics Polymorphism, Single Nucleotide/genetics Risk Assessment
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Do Chuong B
23andMe, Mountain View, California, United States of America. cdo@23andme.com
Tung Joyce Y
Dorfman Elizabeth
Kiefer Amy K
Drabant Emily M
Francke Uta
Mountain Joanna L
Goldman Samuel M
Tanner Caroline M
Langston J William
Wojcicki Anne
Eriksson Nicholas
Conflict of Interest

CBD, JYT, ED, AKK, EMD, UF, JLM, AW, and NE are or have been employed by 23andMe and own stock options in the company. 23andMe CEO AW has provided general guidance, including guidance related to the company's research undertakings and direction. PLoS co-founder Michael B. Eisen is a member of the 23andMe Scientific Advisory Board.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1002141
Email
cdo@23andme.com
Published
2011-06-00
Epub
2011-00-23
Pages
e1002141
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC3121750
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pgen.1002141 PMC Full Text View journal details
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