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Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations

Foo JN 1 , Tan LC 2 , Liany H 1 , Koh TH 1 , Irwan ID 1 , Ng YY 2 Show all authors , Ahmad-Annuar A 3 , Au WL 2 , Aung T 4 , Chan AY 5 , Chong SA 6 , Chung SJ 7 , Jung Y 8 , Khor CC 9 , Kim J 7 , Lee J 10 , Lim SY 11 , Mok V 5 , Prakash KM 2 , Song K 8 , Tai ES 12 , Vithana EN 13 , Wong TY 4 , Tan EK 14 , Liu J 15

Affiliations 

  • 1 Human Genetics, Genome Institute of Singapore, A*STAR, Singapore
  • 2 Department of Neurology, National Neuroscience Institute, Singapore
  • 3 Department of Biomedical Science and
  • 4 Singapore Eye Research Institute, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • 5 Neurology Division, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
  • 6 Institute of Mental Health, Singapore
  • 7 Department of Neurology, Asan Medical Center and
  • 8 Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea
  • 9 Human Genetics, Genome Institute of Singapore, A*STAR, Singapore Singapore Eye Research Institute, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • 10 Institute of Mental Health, Singapore Duke-National University of Singapore Graduate Medical School, Singapore
  • 11 Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 12 Duke-National University of Singapore Graduate Medical School, Singapore Department of Medicine, Yong Loo Lin School of Medicine and Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore
  • 13 Singapore Eye Research Institute, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Duke-National University of Singapore Graduate Medical School, Singapore
  • 14 Department of Neurology, National Neuroscience Institute, Singapore Duke-National University of Singapore Graduate Medical School, Singapore
  • 15 Human Genetics, Genome Institute of Singapore, A*STAR, Singapore Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore liuj3@gis.a-star.edu.sg
Hum Mol Genet, 2014 Jul 15;23(14):3891-7.
PMID: 24565865 DOI: 10.1093/hmg/ddu086

Abstract

To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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