Indirect Genetic Effects of ADIPOQ Variants on Lipid Levels in a Sibling Study of a Rural Chinese Population

Zechen Zhou,Dafang Chen,Zeyu Yan,Xiaoyi Li,Kexin Ding,Yujia Ma,Yiqun Wu,Tao Wu,Han Xiao

doi:10.3390/genes13010161

Abstract

Variations in lipid levels are the result of combinations of genetic and environmental factors. We aim to investigate the indirect effect between siblings of the three polymorphisms of ADIPOQ on serum lipid levels in rural Chinese populations. A total of 2571 sibling pairs were enrolled as study participants. A generalized estimating equation was used to accommodate a family-based design. We used stratified analysis to detect sex combination differences in the indirect genetic effect. We found a significant association between the number of altered risk alleles of rs182052 and ego lipid levels of TG (β = 0.177, P = 0.003), TC (β = 0.140, P = 0.004) and LDL-C (β = 0.098, P = 0.014). Ego and altered genotypes of rs182052 demonstrated a joint effect on ego lipid levels of TC (β = 0.212, P = 0.019), HDL-C (β = 0.099, P = 0.002) and LDL-C (β = 0.177, P = 0.013) in recessive inheritance mode. In opposite-sex siblings, the altered GG genotype of rs182052 increased the ego lipid levels. Thus, our findings demonstrate that ADIPOQ has an indirect genetic effect on lipid levels in sibling pairs, and there are sex-combination differences in the indirect genetic effect in siblings.

Highlights

In the last decade, the prevalence of dyslipidemia has increased significantly [1], while the awareness rate, treatment rate and control rate of dyslipidemia in adults has been low [2]
Mainly triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), are highly heritable, with estimated heritability ranging from 20% to 70% [3]
We found that alter alleles of rs182052 were significantly associated with HDL-C (β = 0.040, P = 0.019), alter alleles of rs266729 were significantly associated with waist circumference (WC) (β = 1.583, P = 0.027) and DBP (β = 1.713, P = 0.020), while the ego alleles showed no significant association

Summary

Introduction

The prevalence of dyslipidemia has increased significantly [1], while the awareness rate, treatment rate and control rate of dyslipidemia in adults has been low [2]. Dyslipidemia is an important component of metabolic syndrome and an important risk factor for atherosclerotic cardiovascular disease. Studying the influencing factors of blood lipid levels is conducive to predicting the occurrence of dyslipidemia and its early intervention, which helps the prevention and treatment of cardiovascular metabolic diseases. Similar to most chronic noncommunicable diseases, variations in lipid levels are the result of combinations of genetic and environmental factors. Mainly triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), are highly heritable, with estimated heritability ranging from 20% to 70% [3]. The mechanisms through which these single nucleotide polymorphisms (SNPs) act on each trait are poorly understood. In terms of environmental factors, many lifestyles can affect lipid levels, including physical inactivity, diets with high positive energy-intake balance due to high-fat or high-glycemic index and alcohol consumption [6,7]

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