Abstract
BackgroundThe genetic contribution to complex diseases or traits, including cardio-metabolic traits, has been elucidated recently by large-scale genome-wide association studies. These genome-wide association studies have indicated that most pleiotropic loci contain genes associated with lipids. Clinically, lipid related abnormalities are strongly associated with other diseases such as type 2 diabetes, coronary artery disease and hypertension. The aim of this study was to evaluate the shared genetic background of lipids and other cardio-metabolic traits.MethodsWe conducted meta-analyses of the association between 157 published lipid-associated loci and 10 cardio-metabolic traits in 14,028 Korean individuals genotyped using the Exome chip (Illumina HumanExome BeadChip). We also examined whether the pleiotropic effects of such loci constituted independent (i.e., biological) pleiotropy or mediated pleiotropy in these metabolic pathways.ResultsEighteen lipid-associated loci were significantly associated with one of six cardio-metabolic traits after correction for multiple testing (P < 3.70 × 10−4). Region 12q24.12 had pleiotropic effects on fasting plasma glucose, blood pressure and obesity-related traits (body mass index and waist-hip ratio) independent of its effects on the lipid profile. Lipid risk scores, calculated according to whether or not subjects carried the risk allele for lipid traits, were significantly associated with fasting plasma glucose, blood pressure and obesity-related traits.ConclusionsThe 12q24.12 region showed ethnic-specific genetic pleiotropy among cardio-metabolic traits in this study. Our findings may help to account for molecular mechanisms based on shared genetic background underlying not only dyslipidemia, but also cardiovascular disease and type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0337-1) contains supplementary material, which is available to authorized users.
Highlights
The genetic contribution to complex diseases or traits, including cardio-metabolic traits, has been elucidated recently by large-scale genome-wide association studies
We aimed to examine the pleiotropic effects of published lipid-associated loci on 10 cardiometabolic traits in a Korean population using data from 14,028 individuals directly genotyped by the Exome chip (Illumina HumanExome BeadChip)
The associations between each of the 135 SNPs and each of the 10 cardio-metabolic traits (TG, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), systolic BP (SBP), diastolic BP (DBP), FPG, HbA1c, Body mass index (BMI) and waist-hip ratio (WHR)) were examined in 14,028 Korean individuals from three cohorts based on Exome chip genotyping
Summary
The genetic contribution to complex diseases or traits, including cardio-metabolic traits, has been elucidated recently by large-scale genome-wide association studies. These genome-wide association studies have indicated that most pleiotropic loci contain genes associated with lipids. The etiology of cardiovascular disease (CVD) is complex, as both genetic and environmental factors contribute [1]. Common risk factors for CVD are cardio-metabolic traits such as lipids, blood pressure, obesity and diabetes [2]. Lipid-related abnormalities are strongly associated with type 2 diabetes (T2D)-related traits and Genetic contributions to complex diseases or traits, including cardio-metabolic traits, have been analyzed by large-scale genome-wide association studies (GWASs). Mediated pleiotropy exists when one genetic variant has an effect on a trait that in turn affects another trait [10]
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