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

Published online by Cambridge University Press:  06 January 2023

Ji Ke
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Wenjing Gao*
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Biqi Wang
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Weihua Cao
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Jun Lv
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Canqing Yu
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Tao Huang
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Dianjianyi Sun
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Chunxiao Liao
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Yuanjie Pang
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Zengchang Pang
Qingdao Municipal Center for Disease Control and Prevention, Qingdao, China
Liming Cong
Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
Hua Wang
Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China
Xianping Wu
Sichuan Center for Disease Control and Prevention, Chengdu, China
Yu Liu
Heilongjiang Provincial Center for Disease Control and Prevention, Harbin, China
Liming Li*
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
Authors for correspondence: Wenjing Gao, Email:; Liming Li, Email:
Authors for correspondence: Wenjing Gao, Email:; Liming Li, Email:
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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 (LOC105378740, LINC02506, CSMD1, MELK, FAM81A, ERAL1 and MIR144) 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 (p < .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.

© The Author(s), 2023. Published by Cambridge University Press on behalf of International Society for Twin Studies

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