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

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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.

authors

  • Holmes, Michael V
  • Lange, Leslie A
  • Palmer, Tom
  • Lanktree, Matthew
  • North, Kari E
  • Almoguera, Berta
  • Buxbaum, Sarah
  • Chandrupatla, Hareesh R
  • Elbers, Clara C
  • Guo, Yiran
  • Hoogeveen, Ron C
  • Li, Jin
  • Li, Yun R
  • Swerdlow, Daniel I
  • Cushman, Mary
  • Price, Tom S
  • Curtis, Sean P
  • Fornage, Myriam
  • Hakonarson, Hakon
  • Patel, Sanjay R
  • Redline, Susan
  • Siscovick, David S
  • Tsai, Michael Y
  • Wilson, James G
  • van der Schouw, Yvonne T
  • FitzGerald, Garret A
  • Hingorani, Aroon D
  • Casas, Juan P
  • de Bakker, Paul IW
  • Rich, Stephen S
  • Schadt, Eric E
  • Asselbergs, Folkert W
  • Reiner, Alex P
  • Keating, Brendan J

publication date

  • February 2014

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