Effects of obesity‐related anthropometric indices and body composition on erectile dysfunction mediated by coronary artery disease: A Mendelian randomization study

孟德尔随机化 医学 人体测量学 内科学 腰围 冠状动脉疾病 肥胖 心脏病学 腰臀比 勃起功能障碍 疾病 随机化 临床试验 生物 遗传学 基因型 遗传变异 基因
作者
Binghao Bao,Jianqiang Guo,Lei Zhang,Zhengkun Pan,Haonan Huang,Zhongjian Qin,Lu Chen,Xiaofeng Zhou,Baoxing Liu
出处
期刊:International Journal of Andrology [Wiley]
卷期号:12 (1): 75-86 被引量:2
标识
DOI:10.1111/andr.13443
摘要

Abstract Background The causal relationship between obesity‐related anthropometric indicators/body composition and erectile dysfunction has not been established in previous observational studies. Method We screened single nucleotide polymorphisms significantly associated with exposure from genome‐wide association studies as instrumental variables ( p < 5.0 × 10 −8 ). The summary statistics for erectile dysfunction were collected from a genome‐wide association study with a sample size of 223,805. Exposure and outcome populations included are of European ancestry. We used univariate and multivariate Mendelian randomization (i) to investigate the causal relationship between genetically predicted obesity‐related anthropometric indicators/body composition and erectile dysfunction and (ii) to examine the mediating role of coronary artery disease. Mendelian randomization analysis was conducted using an inverse variance weighted method. A series of sensitivity analyses validated the results of the Mendelian randomization analysis. Causal estimates are expressed as odds ratios with 95% confidence intervals. Results Obesity‐related anthropometric indicators/body composition were associated with an increased risk of erectile dysfunction in univariate Mendelian randomization analyses. For the 1‐SD increase in body mass index, the odds ratio was 1.841 (95% confidence interval: 1.049–1.355, p = 0.006). For the 1‐SD increase in waist circumference and hip circumference, the odds ratios were 1.275 (95% confidence interval: 1.101–1.478, p = 0.001) and 1.156 (95% confidence interval: 1.015–1.317, p = 0.009), respectively. The odds ratio for the 1‐SD increase in whole body fat mass was 1.221 (95% confidence interval: 1.047–1.388, p = 0.002). For the 1‐SD increase in leg fat percentage (left and right), the odds ratios were 1.256 (95% confidence interval: 1.006–1.567, p = 0.044) and 1.285 (95% confidence interval: 1.027–1.608, p = 0.028), respectively. For the 1‐SD increase in leg fat mass (left and right), the odds ratios were 1.308 (95% confidence interval: 1.108–1.544, p = 0.001) and 1.290 (95% confidence interval: 1.091–1.524, p = 0.003), respectively. For the 1‐SD increase in arm fat mass (left and right), the odds ratios were 1.269 (95% confidence interval: 1.113–1.447, p < 0.001) and 1.254, respectively. Multivariate Mendelian randomization analysis showed that after adjusting for coronary artery disease, some genetic predispositions to obesity‐related anthropometric indicators and body composition were still associated with an increased risk of erectile dysfunction. Significant associations were found for waist circumference–erectile dysfunction (odds ratio: 1.218, 95% confidence interval: 1.036–1.432), leg fat percentage (left)–erectile dysfunction (odds ratio: 1.245, 95% confidence interval: 1.035–1.497), leg fat mass (left)–erectile dysfunction (odds ratio: 1.264, 95% confidence interval: 1.051–1.521), arm fat mass (right)–erectile dysfunction (odds ratio: 1.186, 95% confidence interval: 1.024–1.373), and arm fat mass (left)–erectile dysfunction (odds ratio: 1.17, 95% confidence interval: 1.018–1.360). Meanwhile, coronary artery disease mediated the effects of fat on erectile dysfunction, and the proportion of coronary artery disease‐mediated cases ranged from 10% to 22%. Conclusion There is a potential causal relationship between obesity‐related anthropometric indicators/body composition and erectile dysfunction. Higher waist circumference, leg fat percentage, and arm fat mass may increase the risk of erectile dysfunction, and coronary artery disease partly mediates this overall effect. Understanding the causal relationship between obesity and erectile dysfunction and the mediating role of coronary artery disease may provide more information for erectile dysfunction intervention and prevention strategies.
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