孟德尔随机化
腹部肥胖
因果关系(物理学)
医学
腰围
肥胖
腰臀比
体质指数
内科学
腹部脂肪
人口学
全基因组关联研究
孟德尔遗传
遗传学
生物
单核苷酸多态性
遗传变异
基因
基因型
物理
量子力学
社会学
作者
Germán D. Carrasquilla,Mario García‐Ureña,Shreeya Sharma,Tuomas O. Kilpeläinen
标识
DOI:10.1101/2022.06.06.494971
摘要
Abstract Background and Aims Smokers tend to have a lower body weight than non-smokers, but also more abdominal fat. It remains unclear whether the relationship between smoking and abdominal obesity is causal. Previous Mendelian randomization studies have investigated this relationship by relying on a single genetic variant for smoking heaviness. This approach is sensitive to pleiotropic effects and may produce imprecise causal estimates. We aimed to assess causality between smoking and abdominal obesity using multiple genetic instruments. Methods We used GWAS results for smoking initiation (n=1,232,091), lifetime smoking (n=462,690) and smoking heaviness (n=337,334) as exposure traits, and waist-hip ratio (WHR) and waist and hip circumferences (WC and HC) (n up to 697,734), with and without adjustment for body mass index (adjBMI), as outcome traits. We implemented Mendelian randomization using the CAUSE and LHC-MR methods that instrument smoking using genome-wide data. Results Both CAUSE and LHC-MR indicated a positive causal effect of smoking initiation on WHR (0.13 [95%CI 0.10, 0.16] and 0.49 [0.41, 0.57], respectively) and WHR adjBMI (0.07 [0.03, 0.10] and 0.31 [0.26, 0.37]). Similarly, they indicated a positive causal effect of lifetime smoking on WHR (0.35 [0.29, 0.41] and 0.44 [0.38, 0.51]) and WHR adjBMI (0.18 [0.13, 0.24] and 0.26 [0.20, 0.31]). In follow-up analyses, smoking particularly increased visceral fat. There was no evidence of a mediating role by cortisol or sex hormones. Conclusions Smoking initiation and higher lifetime smoking may lead to abdominal fat distribution. The increase in abdominal fat due to smoking was characterized by an increase in visceral fat. Thus, efforts to prevent and cease smoking can have the added benefit of reducing abdominal fat.
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