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Original Investigation
August 2017

Association of Body Mass Index With Cardiometabolic Disease in the UK BiobankA Mendelian Randomization Study

Author Affiliations
  • 1Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland
  • 2Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Scotland
  • 3Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England
  • 4Medical Research Council Population Health Research Unit, University of Oxford, Oxford, England
  • 5National Institute for Health Research, Oxford Biomedical Research Centre, Oxford University Hospitals, Oxford, England
JAMA Cardiol. 2017;2(8):882-889. doi:10.1001/jamacardio.2016.5804
Key Points

Question  Based on estimates derived using mendelian randomization, what is the association between body mass index and cardiometabolic traits?

Findings  In this population-based cohort study of approximately 120 000 individuals, associations were identified between body mass index and risk of hypertension, coronary heart disease, type 2 diabetes, and elevated systolic and diastolic blood pressures. No associations between body mass index and stroke or pulse rate were observed.

Meaning  Body mass index represents an important modifiable factor for ameliorating the risk of cardiometabolic disease in the general population.


Importance  Higher body mass index (BMI) is a risk factor for cardiometabolic disease; however, the underlying causal associations remain unclear.

Objectives  To use UK Biobank data to report causal estimates of the association between BMI and cardiometabolic disease outcomes and traits, such as pulse rate, using mendelian randomization.

Design, Setting, and Participants  Cross-sectional baseline data from a population-based cohort study including 119 859 UK Biobank participants with complete phenotypic (medical and sociodemographic) and genetic data. Participants attended 1 of 22 assessment centers across the United Kingdom between 2006 and 2010. The present study was conducted from May 1 to July 11, 2016.

Main Outcomes and Measures  Prevalence of hypertension, coronary heart disease, and type 2 diabetes were determined at assessment, based on self-report. Blood pressure was measured clinically. Participants self-reported sociodemographic information pertaining to relevant confounders. A polygenic risk score comprising 93 single-nucleotide polymorphisms associated with BMI from previous genome-wide association studies was constructed, and the genetic risk score was applied to derive causal estimates using a mendelian randomization approach.

Results  Of the 119 859 individuals included in the study, 56 816 (47.4%) were men; mean (SD) age was 56.87 (7.93) years. Mendelian randomization analysis showed significant positive associations between genetically instrumented higher BMI and risk of hypertension (odds ratio [OR] per 1-SD higher BMI, 1.64; 95% CI, 1.48-1.83; P = 1.1 × 10−19), coronary heart disease (OR, 1.35; 95% CI, 1.09-1.69; P = .007) and type 2 diabetes (OR, 2.53; 95% CI, 2.04-3.13; P = 1.5 × 10−17), as well as systolic blood pressure (β = 1.65 mm Hg; 95% CI, 0.78-2.52 mm Hg; P = 2.0 × 10−04) and diastolic blood pressure (β  = 1.37 mm Hg; 95% CI, 0.88-1.85 mm Hg; P = 3.6 × 10−08). These associations were independent of age, sex, Townsend deprivation scores, alcohol intake, and smoking history.

Conclusions and Relevance  The results of this study add to the burgeoning evidence of an association between higher BMI and increased risk of cardiometabolic diseases. This finding has relevance for public health policies in many countries with increasing obesity levels.