Genomics Inform.  2019 Dec;17(4):e48. 10.5808/GI.2019.17.4.e48.

Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians

• Choi JY
• Jang HM
• Han S
• Hwang MY
• Kim BJ
• Kim YJ

• KMID: 2468874
• DOI: http://doi.org/10.5808/GI.2019.17.4.e48

Abstract

Over the last decade, genome-wide association studies (GWASs) have provided an unprecedented amount of genetic variations that are associated with various phenotypes. However, previous GWAS were mostly conducted in European populations, and these biased results for non-Europeans may result in a significant reduction in risk prediction for non-Europeans. An issue with the early GWAS was the winner's curse problem, which led to misleading results when constructing the polygenic risk scores (PRS). Therefore, more non-European population-based studies are needed to validate reported variants and improve genetic risk assessment across diverse populations. In this study, we validated 422 variants independently associated with glycemic indexes, liver enzymes, and type 2 diabetes in 125,872 samples from a Korean population, and further validated the results by assessing publicly available summary statistics from European GWAS (n = 898,130). Among the 422 independently associated variants, 284, 320, and 361 variants were replicated in Koreans, Europeans, and either one of the two populations. In addition, the effect sizes for Koreans and Europeans were moderately correlated (r = 0.33-0.68). However, 61 variants were not replicated in both Koreans and Europeans. Our findings provide valuable information on effect sizes and statistical significance, which is essential to improve the assessment of disease risk using PRS analysis.

Keyword

genome-wide association study; glycemic index; phenotype; single nucleotide polymorphism; type 2 diabetes

MeSH Terms

Asian Continental Ancestry Group*
Bias (Epidemiology)
Genetic Variation
Genome-Wide Association Study
Glycemic Index
Humans
Liver
Phenotype
Polymorphism, Single Nucleotide
Risk Assessment