肥胖(腰围,身体质量指数(BMI))和生活方式因素(饮食习惯,吸烟,饮酒,在观察性研究中,久坐行为)与良性前列腺增生(BPH)的风险有关,但这些关联是否是因果关系尚不清楚.
我们进行了单变量和多变量孟德尔随机化研究来评估这些关联。从相应的全基因组关联研究(n=216,590至1,232,091个人)中选择了与全基因组显著性水平(P<5×10-8)的暴露相关的遗传工具。BPH的汇总数据来自英国生物银行(14,126例和169,762例非病例)和FinnGen联盟(13,118例和72,799例非病例)。英国生物银行和FinnGen联盟的结果使用固定效应荟萃分析进行组合。
BPH的综合比值比(OR)为1.24(95%置信区间(CI),1.07-1.43,P=0.0045),1.08(95%CI1.01-1.17,P=0.0175),0.94(95%CI0.67-1.30,P=0.6891),1.29(95%CI0.88-1.89,P=0.1922),1.23(95%CI0.85-1.78,P=0.2623),腰围增加一个标准差(SD)为1.04(95%CI0.76-1.42,P=0.8165),BMI,和相对碳水化合物,脂肪,蛋白质和糖的摄入量,1.05(95%CI0.92-1.20,P=0.4581),吸烟开始的患病率增加了一个SD,1.10(95%CI0.96-1.26,P=0.1725)和0.84(95%CI0.69-1.02,P=0.0741)每天对数转换吸烟和每周饮料增加一个SD,和1.31(95%CI1.08-1.58,P=0.0051),久坐行为增加一个SD。遗传预测的腰围(OR=1.26,95%CI1.11-1.43,P=0.0004)和久坐行为(OR=1.14,95%CI1.05-1.23,P=0.0021)与调整BMI后的BPH相关。
这项研究支持高腰围的独立因果作用,BPH的BMI和久坐行为。
Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear.
We performed a univariable and multivariable Mendelian randomization
study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis.
The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI.
This
study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.