Ethnicity- and Sex-Specific Genome-Wide Association Study on Parkinson’s Disease

Abstract Most previous genome-wide association studies (GWASs) on Parkinson’s disease (PD) focus on the European population. There are several sex-specific clinical differences in PD, but little is known about its genetic background. In this study, we aimed to perform an ethnicity-specific, and sex-specific GWAS on PD in the Korean population. A total of 1,050 Korean PD patients and 5,000 controls were included. For primary analysis, we performed a GWAS using a logistic additive model adjusted for age and sex. Same statistical models were also applied to sex-specific analyses. Genotyping was performed using a customized microarray chip that is optimal for the Korean population. Nine single nucleotide polymorphisms (SNPs) including four in the SNCA locus and three from the PARK16 locus were associated with PD in Koreans. The rs34778348 in the LRRK2 locus showed a strong association, though failed to pass cluster quality control. There were no notable genome-wide significant markers near the MAPT or GBA loci. In the female-only analysis, rs34778348 in LRRK2 and the four other SNPs in the SNCA showed strong association with PD. In the male-only analysis, no SNP surpassed the genome-wide significance threshold under Bonferroni correction; however, the most significant signal was rs708726 in the PARK16 locus. This ethnicity- and sex-specific GWAS on PD implicates the pan-ethnic effect of SNCA, universal but East-Asian inclined effect of PARK16, East Asian-specific role of LRRK2 G2385R variants, and the possible disproportionate effect of SNCA and PARK16 between sexes for PD susceptibility. These findings suggest the different genetic contributions to sporadic PD in terms of ethnicity and sex.