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Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank: A Mendelian Randomization Study.
JAMA Cardiol 2017; 2(8):882-889JC

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.

Authors+Show Affiliations

Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland.Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Scotland.Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland.Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Scotland.Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland.Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Scotland.Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland.Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Scotland.Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland.Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England. Medical Research Council Population Health Research Unit, University of Oxford, Oxford, England. National Institute for Health Research, Oxford Biomedical Research Centre, Oxford University Hospitals, Oxford, England.Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow Scotland.Institute of Health & Wellbeing, University of Glasgow, Glasgow, Scotland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28678979

Citation

Lyall, Donald M., et al. "Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank: a Mendelian Randomization Study." JAMA Cardiology, vol. 2, no. 8, 2017, pp. 882-889.
Lyall DM, Celis-Morales C, Ward J, et al. Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank: A Mendelian Randomization Study. JAMA Cardiol. 2017;2(8):882-889.
Lyall, D. M., Celis-Morales, C., Ward, J., Iliodromiti, S., Anderson, J. J., Gill, J. M. R., ... Pell, J. P. (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.
Lyall DM, et al. Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank: a Mendelian Randomization Study. JAMA Cardiol. 2017 08 1;2(8):882-889. PubMed PMID: 28678979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank: A Mendelian Randomization Study. AU - Lyall,Donald M, AU - Celis-Morales,Carlos, AU - Ward,Joey, AU - Iliodromiti,Stamatina, AU - Anderson,Jana J, AU - Gill,Jason M R, AU - Smith,Daniel J, AU - Ntuk,Uduakobong Efanga, AU - Mackay,Daniel F, AU - Holmes,Michael V, AU - Sattar,Naveed, AU - Pell,Jill P, PY - 2017/7/6/pubmed PY - 2019/6/4/medline PY - 2017/7/6/entrez SP - 882 EP - 889 JF - JAMA cardiology JO - JAMA Cardiol VL - 2 IS - 8 N2 - 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. SN - 2380-6591 UR - https://www.unboundmedicine.com/medline/citation/28678979/Association_of_Body_Mass_Index_With_Cardiometabolic_Disease_in_the_UK_Biobank:_A_Mendelian_Randomization_Study_ L2 - https://jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2016.5804 DB - PRIME DP - Unbound Medicine ER -