Exome chip‐driven association study of lipidemia in >14,000 Koreans and evaluation of genetic effect on identified variants between different ethnic groups

Abstract

Lipid levels in blood are widely used to diagnose and monitor chronic diseases. It is essential to identify the genetic traits involved in lipid metabolism for understanding chronic diseases. However, the influence of genetic traits varies depending on race, sex, age, and ethnicity. Therefore, research focusing on populations of individual countries is required, and the results can be used as a basis for comparison of results of other studies at the cross-racial and crosscountry levels. In the present study, we selected lipid-related variants and evaluated their effects on lipid-related diseases in more than 14,000 subjects of three cohorts using the Illumina Human Exome Beadchip. A genome-wide association study was conducted using EPACTs after adjusting for age, sex, and recruitment area. A genome-wide significance cutoff was defined as p < 5E−08 in all the three cohorts. Sixteen variants represented the lipid traits and were classified as vulnerable to borderline hypertriglyceridemia, hyper-LDL-cholesterolemia, or hypo-HDL-cholesterolemia. Moreover, we compared the genetic effects of the 16 variants between ethnic groups and identified the missense variants in apolipoprotein A-V, cholesterol ester transfer protein, and apolipoprotein E as Asian-specific. Our study provides candidate genes as markers for chronic diseases through the evaluation of genetic effects.

Genetics of Familial Hypercholesterolemia: New Insights

“…For example, in the Japanese population ( Tada et al, 2018 ), variants within the ABO gene have been identified as significantly modifying plasma lipoprotein metabolism, while “the usual suspects” (genes for SORT-1 , LDLR and HMGCR ) showed rather negligible effects. Importantly, identical variants could have different effects on plasma lipids and the frequencies of genetic variants can differ between different ethnicities ( Han et al, 2019 ); thus, a different gene score should be introduced for populations of different ethnic backgrounds.…”