Analysis of non-synonymous-coding variants of Parkinson%26apos;s disease-related pathogenic and susceptibility genes in East Asian populations

作者：Foo Jia Nee; Tan Louis C; Liany Herty; Koh Tat Hung; Irwan Ishak D; Ng Yen Yek; Ahmad Annuar Azlina; Au Wing Lok; Aung Tin; Chan Anne Y Y; Chong Siow Ann; Chung Sun Ju; Jung Yusun; Khor Chiea Chuen; Kim Juyeon; Lee Jimmy; Lim Shen Yang; Mok Vincent; Prakash Kumar M; Song Kyuyoung; Tai E Shyong; Vithana Eranga N; Wong Tien Yin; Tan Eng King; Liu Jianjun^*

来源：Human Molecular Genetics, 2014, 23(14): 3891-3897.

DOI：10.1093/hmg/ddu086

To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson%26apos;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 x 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.

• 出版日期2014-7-15
• 单位香港中文大学