Gene-obesogenic environment interactions in the UK Biobank study.

• Type of Material: Article
• Authors: Jessica Tyrrell, University of Exeter; Andrew R. Wood, University of Exeter; Ryan M. Ames, University of Exeter; Hanieh Yaghootkar, University of Exeter; Robin N. Beaumont, University of Exeter; Samuel E. Jones, University of Exeter; Marcus A. Tuke, University of Exeter; Katherine S. Ruth, University of Exeter; Rachel M. Freathy, University of Exeter; George Davey Smith, University of Bristol; Stephane Joost, Ecole Polytechnique Fédérale de Lausanne (EPFL); Idris Guessous, Emory University; Anna Murray, University of Exeter; David P. Strachan, St George’s, University of London; Zoltan Kutalik, Lausanne University Hospital (CHUV); Michael N. Weedon, University of Exeter; Timothy M. Frayling, University of Exeter
• Language: English
• Date: 2017-04-01
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option D
• Publication Version: Final Published Version
• Copyright Statement: © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/ije/dyw337
• Title of Journal or Parent Work: International Journal of Epidemiology
• ISSN: 0300-5771
• Volume: 46
• Issue: 2
• Start Page: 559
• End Page: 575
• Grant/Funding Information: A.R.W., H.Y. and T.M.F. are supported by the European Research Council grant: 323195:SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC.; M.A.T., M.N.W. and A.M. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF).; Z.K. is funded by Swiss National Science Foundation (31003A-143914).; R.B. is funded by the Wellcome Trust and Royal Society grant: 104150/Z/14/Z.; R.M.F. is a Sir Henry Dale Fellow (Wellcome Trust and Royal Society grant: 104150/Z/14/Z).; R.M.A is supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA).; J.T. is funded by a Diabetes Research and Wellness Foundation Fellowship.; The funders had no influence on study design, data collection and analysis, decision to publish or preparation of the manuscript.; S.E.J. is funded by the Medical Research Council (grant: MR/M005070/1).
• Keywords: body mass index; gene–environment; social deprivation; UK Biobank; obesogenic environment
• Research Categories: Health Sciences, Epidemiology; Health Sciences, General

Abstract

Background: Previous studies have suggested that modern obesogenic environments accentuate the genetic risk of obesity. However, these studies have proven controversial as to which, if any, measures of the environment accentuate genetic susceptibility to high body mass index (BMI). Methods: We used up to 120 000 adults from the UK Biobank study to test the hypothesis that high-risk obesogenic environments and behaviours accentuate genetic susceptibility to obesity. We used BMI as the outcome and a 69-variant genetic risk score (GRS) for obesity and 12 measures of the obesogenic environment as exposures. These measures included Townsend deprivation index (TDI) as a measure of socio-economic position, TV watching, a 'Westernized' diet and physical activity. We performed several negative control tests, including randomly selecting groups of different average BMIs, using a simulated environment and including sun-protection use as an environment. Results: We found gene-environment interactions with TDI (Pinteraction = 3 × 10 -10 ), self-reported TV watching (Pinteraction = 7 × 10 -5 ) and self-reported physical activity (Pinteraction = 5 × 10 -6 ). Within the group of 50% living in the most relatively deprived situations, carrying 10 additional BMI-raising alleles was associated with approximately 3.8 kg extra weight in someone 1.73 m tall. In contrast, within the group of 50% living in the least deprivation, carrying 10 additional BMI-raising alleles was associated with approximately 2.9 kg extra weight. The interactions were weaker, but present, with the negative controls, including sun-protection use, indicating that residual confounding is likely. Conclusions: Our findings suggest that the obesogenic environment accentuates the risk of obesity in genetically susceptible adults. Of the factors we tested, relative social deprivation best captures the aspects of the obesogenic environment responsible.