Association of body mass index with cardiometabolic disease in the UK Biobank: a Mendelian randomization study

Lyall, D. M. et al. (2017) Association of body mass index with cardiometabolic disease in the UK Biobank: a Mendelian randomization study. JAMA Cardiology, 2(8), pp. 882-889. (doi: 10.1001/jamacardio.2016.5804) (PMID:28678979) (PMCID:PMC5710596)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gill, Professor Jason and Smith, Professor Daniel and Anderson, Dr Jana and Mackay, Professor Daniel and Ntuk, Uduakobong Efanga and Ward, Dr Joey and Celis, Dr Carlos and Iliodromiti, Dr Stamatina and Pell, Professor Jill and Sattar, Professor Naveed and Lyall, Dr Donald
• Authors: Lyall, D. M., Celis-Morales, C., Ward, J., Iliodromiti, S., Anderson, J. J., Gill, J. M.R., Smith, D. J., Ntuk, U. E., Mackay, D. F., Holmes, M. V., Sattar, N., and Pell, J. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: JAMA Cardiology
• Publisher: American Medical Association
• ISSN: 2380-6583
• ISSN (Online): 2380-6591
• Published Online: 05 July 2017
• Copyright Holders: Copyright © 2017 American Medical Association
• First Published: First published in JAMA Cardiology 2(8): 882-889
• Publisher Policy: Reproduced in accordance with the publisher copyright policy