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Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis.

Abstract：

: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 kg/m(2) genetically elevated BMI increased fasting glucose (0.18 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 mmHg; 95% CI = 0.24-1.16) and reduced high-density lipoprotein cholesterol (-0.02 mmol/l; 95% CI = -0.03 to -0.01) and low-density lipoprotein cholesterol (LDL-C; -0.04 mmol/l; 95% CI = -0.07 to -0.01). Observational and causal estimates were directionally concordant, except for LDL-C. A 1 kg/m(2) 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 kg/m(2) 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.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Holmes MV,Lange LA,Palmer T,Lanktree MB,North KE,Almoguera B,Buxbaum S,Chandrupatla HR,Elbers CC,Guo Y,Hoogeveen RC,Li J,Li YR,Swerdlow DI,Cushman M,Price TS,Curtis SP,Fornage M,Hakonarson H,Patel SR,Redline S,S

doi

10.1016/j.ajhg.2013.12.014

subject

Has Abstract

pub_date

2014-02-06 00:00:00

pages

198-208

issue

2

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(13)00584-3

journal_volume

94

pub_type

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