孟德尔随机化
痛风
肥胖
内科学
医学
高尿酸血症
内分泌学
尿酸
胃肠病学
基因型
生物
遗传学
基因
遗传变异
作者
Charleen D. Adams,Brian B. Boutwell
标识
DOI:10.1038/s41598-021-97410-4
摘要
Abstract Observational studies suggest relationships between obesity, urate, and gout but are possibly confounded. We assessed whether genetically determined obesity, higher urate (and related traits), and gout were causal using multiple Mendelian randomization (MR) approaches and linkage disequilibrium score regression for genetic correlations ( r g ). For data, we used genome-wide association study summary statistics available through MR-Base. We observed that obesity increased urate (beta = 0.127; 95% CI = 0.098, 0.157; P -value = 1.2E−17; r g = 0.25 [ P -value = 0.001]) and triglycerides (beta = 0.082; 95% CI = 0.065, 0.099; P -value = 1.2E−21; r g = 0.23 [ P -value = 8.8E−12]) and decreased high-density lipoprotein cholesterol (HDL) (beta = − 0.083; 95% CI = − 0.101, − 0.065; P -value = 2.5E−19; r g = − 0.28; [ P -value = 5.2E−24]). Higher triglycerides increased urate (beta = 0.198; 95% CI = 0.146, 0.251; P -value = 8.9E−14; r g = 0.29 [ P -value = 0.001]) and higher HDL decreased urate (beta = − 0.109; 95% CI = − 0.148, − 0.071; P -value = 2.7E− 08; r g = − 0.21 [ P -value = 9.8E−05]). Higher urate (OR = 1.030; 95% CI = 1.028, 1.032; P -value = 1.1E−130; r g = 0.89 [ P -value = 1.7E−55]) and obesity caused gout (OR = 1.003; 95% CI = 1.001, 1.004; P -value = 1.3E−04; r g = 0.23 [ P -value = 2.7E−05]). Obesity on gout with urate as a mediator revealed all the effect of obesity on gout occurred through urate. Obesity on low-density lipoprotein cholesterol (LDL) was null (beta = −0.011; 95% CI = −0.030, 0.008; P -value = 2.6E−01; r g = 0.03 [ P -value = 0.369]). A multivariable MR of obesity, HDL, and triglycerides on urate showed obesity influenced urate when accounting for HDL and triglycerides. Obesity’s impact on urate was exacerbated by it decreasing HDL.
科研通智能强力驱动
Strongly Powered by AbleSci AI