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利用双变量方法探索肥胖与血清脂质水平的遗传关联。

Exploring the Genetic Association between Obesity and Serum Lipid Levels Using Bivariate Methods.

机构信息

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Qingdao Municipal Center for Disease Control and Prevention, Qingdao, China.

出版信息

Twin Res Hum Genet. 2022 Dec;25(6):234-244. doi: 10.1017/thg.2022.39. Epub 2023 Jan 6.

Abstract

It is crucial to understand the genetic mechanisms and biological pathways underlying the relationship between obesity and serum lipid levels. Structural equation models (SEMs) were constructed to calculate heritability for body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the genetic connections between BMI and the four classes of lipids using 1197 pairs of twins from the Chinese National Twin Registry (CNTR). Bivariate genomewide association studies (GWAS) were performed to identify genetic variants associated with BMI and lipids using the records of 457 individuals, and the results were further validated in 289 individuals. The genetic background affecting BMI may differ by gender, and the heritability of males and females was 71% (95% CI [.66, .75]) and 39% (95% CI [.15, .71]) respectively. BMI was positively correlated with TC, TG and LDL-C in phenotypic and genetic correlation, while negatively correlated with HDL-C. There were gender differences in the correlation between BMI and lipids. Bivariate GWAS analysis and validation stage found 7 genes (, , , , , and ) that were possibly related to BMI and lipid levels. The significant biological pathways were the regulation of cholesterol reverse transport and the regulation of high-density lipoprotein particle clearance ( < .001). BMI and blood lipid levels were affected by genetic factors, and they were genetically correlated. There might be gender differences in their genetic correlation. Bivariate GWAS analysis found MIR144 gene and its related biological pathways may influence obesity and lipid levels.

摘要

了解肥胖症与血清脂质水平之间关系的遗传机制和生物学途径至关重要。使用来自中国国家双胞胎登记处(CNTR)的 1197 对双胞胎,构建结构方程模型(SEMs)以计算体重指数(BMI)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)的遗传率,以及 BMI 与四类脂质之间的遗传联系。使用 457 个人的记录进行双变量全基因组关联研究(GWAS),以鉴定与 BMI 和脂质相关的遗传变异,并在 289 个人中进一步验证。影响 BMI 的遗传背景可能因性别而异,男性和女性的遗传率分别为 71%(95%CI [.66,.75])和 39%(95%CI [.15,.71])。在表型和遗传相关中,BMI 与 TC、TG 和 LDL-C 呈正相关,与 HDL-C 呈负相关。BMI 与血脂之间的相关性存在性别差异。双变量 GWAS 分析和验证阶段发现 7 个可能与 BMI 和血脂水平相关的基因(、、、、、和)。显著的生物学途径是胆固醇逆向转运的调节和高密度脂蛋白颗粒清除的调节(<0.001)。BMI 和血脂水平受遗传因素影响,它们在遗传上相关。它们的遗传相关性可能存在性别差异。双变量 GWAS 分析发现 MIR144 基因及其相关的生物学途径可能影响肥胖症和血脂水平。

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