Causal Effects of Body Mass Index on Cardiometabolic Traits and Events: A Mendelian Randomization Analysis

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• 作者：Michael聽V. Holmes ; Leslie聽A. Lange ; Tom Palmer ; Matthew聽B. Lanktree ; Kari聽E. North ; Berta Almoguera ; Sarah Buxbaum ; Hareesh聽R. Ch ; rupatla ; Clara聽C. Elbers ; Yiran Guo ; Ron聽C. Hoogeveen ; Jin Li ; Yun聽R. Li ; Daniel聽I. Swerdlow ; Mary Cushman ; Tom聽S. Price ; Sean聽P. Curtis ; Myriam Fornage ; Hakon Hakonarson ; Sanjay聽R. Patel ; Susan Redline ; et al.
• 刊名：The American Journal of Human Genetics
• 出版年：6 February, 2014
• 年：2014
• 卷：94
• 期：2
• 页码：198-208
• 全文大小：628 K

文摘

Elevated body mass index (BMI) associates with cardiometabolic traits on observational analysis, yet the underlying causal relationships remain unclear. We conducted Mendelian randomization analyses by using a genetic score (GS) comprising 14 BMI-associated SNPs from a recent discovery analysis to investigate the causal role of BMI in cardiometabolic traits and events. We used eight population-based cohorts, including 34,538 European-descent individuals (4,407 type 2 diabetes (T2D), 6,073 coronary heart disease (CHD), and 3,813 stroke cases). A 1聽kg/m² genetically elevated BMI increased fasting glucose (0.18聽mmol/l; 95% confidence interval (CI) = 0.12-0.24), fasting insulin (8.5%; 95% CI = 5.9-11.1), interleukin-6 (7.0%; 95% CI = 4.0-10.1), and systolic blood pressure (0.70聽mmHg; 95% CI聽= 0.24-1.16) and reduced high-density lipoprotein cholesterol (鈭?.02聽mmol/l; 95% CI = 鈭?.03 to 鈭?.01) and low-density lipoprotein cholesterol (LDL-C; 鈭?.04聽mmol/l; 95% CI = 鈭?.07 to 鈭?.01). Observational and causal estimates were directionally concordant, except for LDL-C. A 1聽kg/m² genetically elevated BMI increased the odds of T2D (odds ratio [OR] = 1.27; 95% CI = 1.18-1.36) but did not alter risk of CHD (OR 1.01; 95% CI = 0.94-1.08) or stroke (OR = 1.03; 95% CI = 0.95-1.12). A meta-analysis incorporating published studies reporting 27,465 CHD events in 219,423 individuals yielded a pooled OR of 1.04 (95% CI = 0.97-1.12) per 1聽kg/m² increase in BMI. In conclusion, we identified causal effects of BMI on several cardiometabolic traits; however, whether BMI causally impacts CHD risk requires further evidence.