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Cited by 515Parkinson's Disease Mechanisms and TreatmentsGenetic Associations and EpidemiologyNuclear Receptors and Signaling

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

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Do, Chuong B., Tung, Joyce Y., Dorfman, Elizabeth, Kiefer, Amy K., Drabant, Emily M., Francke, Uta, Mountain, Joanna L., Goldman, Samuel M. +4 more·2011·PLoS Genetics
DOI 10.1371/journal.pgen.1002141PMC PMC3121750
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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.

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Cited by

Sorted by citations

Authors
Do, C. B., Tung, J. Y., Dorfman, E., Kiefer, A. K., Drabant, E. M., Francke, U., Mountain, J. L., Goldman, S. M., Tanner, C. M., Langston, J. W., Wojcicki, A., & Eriksson, N.
Affiliations
  • 23andMe (United States) (US)
  • Parkinson's Institute and Clinical Center (US)
Corresponding author
  • Do, Chuong B.
  • Eriksson, Nicholas
ORCID
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2011-06-23
Volume
7
Issue
6
Pages
e1002141
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1002141
PMC
PMC3121750
OpenAlex
W2144037754
Cited by
515
References
5
Citations by year
2026: 7 · 2025: 20 · 2024: 13 · 2023: 15 · 2022: 27 · 2021: 34 · 2020: 35 · 2019: 28 · 2018: 39 · 2017: 32 · 2016: 38 · 2015: 54 · 2014: 48 · 2013: 52 · 2012: 58
FWCI
34.94
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
Funders
  • Michael J. Fox Foundation for Parkinson's Research
  • Parkinson's Foundation
  • NIH Clinical Center
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, genetic susceptibility, genome-wide association study, SCARB2, heritability, LRRK2, glucocerebrosidase, SNCA, MAPT, GAK, HLA region, early-onset Parkinson's disease, late-onset Parkinson's disease
MeSH terms
Humans, Parkinson Disease, Databases, Factual, Risk Assessment, Genetic Predisposition to Disease, Internet, Polymorphism, Single Nucleotide, Heredity, Genome-Wide Association Study, Genetic Loci

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