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Causal effects of body mass index on cardiometabolic traits and events : a mendelian randomization analysis
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(2014) Causal effects of body mass index on cardiometabolic traits and events : a mendelian randomization analysis. The American Journal of Human Genetics, Volume 94 (Number 2). pp. 198-208. doi:10.1016/j.ajhg.2013.12.014 ISSN 0002-9297.
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Official URL: http://dx.doi.org/10.1016/j.ajhg.2013.12.014
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/m2 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/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 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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | The American Journal of Human Genetics | ||||
| Publisher: | Cell Press | ||||
| ISSN: | 0002-9297 | ||||
| Official Date: | 6 February 2014 | ||||
| Dates: |
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| Volume: | Volume 94 | ||||
| Number: | Number 2 | ||||
| Page Range: | pp. 198-208 | ||||
| DOI: | 10.1016/j.ajhg.2013.12.014 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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