Genome wide association study using direct-to-consumer genetic testing data and online survey approach in Han Chinese participants among WeGene users, a proof-of-concept study

【摘要】：The growing number of genotyped individuals from direct-to-consumer(DTC) genetic testing and the advent of high-throughput phenotyping techniques have rapidly accelerated the accumulation of personal genome data. By using online survey and self-report measures, we were able to rapidly and inexpensively ascertain a large number of participants among DTC genetic testing consumers. To test this proof-of-concept study model in China, we performed a genome-wide association study(GWAS) of 16 self-reported traits in 12,256 Han Chinese individuals among WeGene users. Of these, we identified the most robust and replicated alleles rs671 in ALDH2 in East Asian ancestry populations map to alcohol-related traits("alcohol flush" P = 8.34×10~(-27); "AUDIT section score" P = 1.09×10~(-20); and "amount of daily drink", P = 2.88×10~(-17)). Petaloid toenail, the nail of little toe appears petaloidly exists in many populations of the Han Nationality in North China, was associated with a loci of genome-wide significance at 5 q14 lead by rs988056(P = 9.10×10~(-9) in "left-sided petaloid toenail"; P = 1.31×10~(-8) in "petaloid toenail number" traits) near PITX1, which has been associated with asymmetric lower-limb malformations. No genome-wide significant signals(threshold P 5×10~(-8)) but only some suggestive association(threshold P 1×10~(-5)) were found in the rest traits, probably due to the complex inheritance patterns of these traits and/or the limited sample size of this pilot study. We conclude that conducting a genetic study using responses to an online questionnaire in a large population of DTC genetic testing consumers may represent a cost-effective strategy to investigate various traits in Chinese populations. Our findings will contribute to future studies of non-European populations and serve as a fundamental resource for understanding the genetics and biology underlying human traits.