title: Gene-obesogenic environment interactions in the UK Biobank study.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.|European Centre for Environment and Human Health, University of Exeter Medical School, The Knowledge Spa, Truro, TR1 3HD, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Tyrrell
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Wood
authors.affiliation: Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Exeter, RILD Level 3, Exeter, EX2 5DW, UK.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Ames
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Hanieh
authors.initials: H
authors.lastname: Yaghootkar
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Robin N
authors.initials: RN
authors.lastname: Beaumont
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Jones
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Tuke
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Ruth
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.|Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.affiliation: Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Laboratory of Geographical Information Systems (LASIG), School of Architecture, Civil and Environmental Engineering (ENAC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Joost
authors.affiliation: Unit of Population Epidemiology, Division of Primary Care Medicine, Department of Community Medicine, Primary Care and Emergency Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.|Department of Ambulatory care and Community medicine, University of Lausanne, Lausanne, Switzerland.|Department of Epidemiology, Emory University, Atlanta, GA, USA.
authors.forename: Idris
authors.initials: I
authors.lastname: Guessous
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Murray
authors.affiliation: Population Health Research Institute, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.affiliation: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital (CHUV), Lausanne, Switzerland and.|Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, UK.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
mesh_terms: D000328:Adult; D000368:Aged; D018070:Biological Specimen Banks; D015992:Body Mass Index; D004032:Diet; D004777:Environment; D015444:Exercise; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D057185:Sedentary Behavior; D006113:United Kingdom
keywords: UK Biobank; body mass index; gene–environment; obesogenic environment; social deprivation