@article{JTyrrell2016,
title = {Gene–obesogenic environment interactions in the UK Biobank study},
author = {Jessica Tyrrell, and Timothy M Frayling
},
url = {http://ije.oxfordjournals.org/content/early/2017/01/10/ije.dyw337.full.pdf+html},
year = {2017},
date = {2017-01-11},
journal = {International Journal of Epidemiology},
abstract = {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 (Pinteraction¼ 3 10–10), self-reported TV watching (Pinteraction ¼ 7 10–5) and self-reported physical activity (Pinteraction¼ 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.
},
note = {Jessica Tyrrell, Andrew R Wood, Ryan M Ames,
Hanieh Yaghootkar, Robin N Beaumont, Samuel E Jones,
Marcus A Tuke, Katherine S Ruth, Rachel M Freathy,
George Davey Smith, Stephane Joost, Idris Guessous,
Anna Murray, David P Strachan, Zoltan Kutalik,
Michael N Weedon1 and Timothy M Frayling1*
},
keywords = {body mass index, featured, gene–environment, obesogenic environment, social deprivation},
pubstate = {published},
tppubtype = {article}
}

@article{AlexanderIYoung2016,
title = {Multiple novel gene-by-environment interactions modify the effect of FTO variants on body mass index},
author = {Alexander I. Young, Fabian Wauthier, Peter Donnelly},
url = {http://www.nature.com/articles/ncomms12724},
year = {2016},
date = {2016-09-06},
journal = {Nature Communications},
abstract = {Genetic studies have shown that obesity risk is heritable and that, of the many common variants now associated with body mass index, those in an intron of the fat mass and obesity-associated (FTO) gene have the largest effect. The size of the UK Biobank, and its joint measurement of genetic, anthropometric and lifestyle variables, offers an unprecedented opportunity to assess gene-by-environment interactions in a way that accounts for the dependence between different factors. We jointly examine the evidence for interactions between FTO (rs1421085) and various lifestyle and environmental factors. We report interactions between the FTO variant and each of: frequency of alcohol consumption (P=3.0 × 10−4); deviations from mean sleep duration (P=8.0 × 10−4); overall diet (P=5.0 × 10−6), including added salt (P=1.2 × 10−3); and physical activity (P=3.1 × 10−4).},
keywords = {body mass index, featured, FTO, gene-by-environment},
pubstate = {published},
tppubtype = {article}
}

@article{tyrrellJ2016b,
title = {Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight},
author = {Tyrrell, J.
Richmond, R. C.
Palmer, T. M.
Feenstra, B.
Rangarajan, J.
Metrustry, S.
Cavadino, A.
Paternoster, L.
Armstrong, L. L.
De Silva, N. M.
Wood, A. R.
Horikoshi, M.
Geller, F.
Myhre, R.
Bradfield, J. P.
Kreiner-Moller, E.
Huikari, V.
Painter, J. N.
Hottenga, J. J.
Allard, C.
Berry, D. J.
Bouchard, L.
Das, S.
Evans, D. M.
Hakonarson, H.
Hayes, M. G.
Heikkinen, J.
Hofman, A.
Knight, B.
Lind, P. A.
McCarthy, M. I.
McMahon, G.
Medland, S. E.
Melbye, M.
Morris, A. P.
Nodzenski, M.
Reichetzeder, C.
Ring, S. M.
Sebert, S.
Sengpiel, V.
Sorensen, T. I.
Willemsen, G.
de Geus, E. J.
Martin, N. G.
Spector, T. D.
Power, C.
Jarvelin, M. R.
Bisgaard, H.
Grant, S. F.
Nohr, E. A.
Jaddoe, V. W.
Jacobsson, B.
Murray, J. C.
Hocher, B.
Hattersley, A. T.
Scholtens, D. M.
Davey Smith, G.
Hivert, M. F.
Felix, J. F.
Hypponen, E.
Lowe, W. L., Jr.
Frayling, T. M.
Lawlor, D. A.
Freathy, R. M.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26978208},
year = {2016},
date = {2016-03-16},
journal = {JAMA},
abstract = {IMPORTANCE: Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. OBJECTIVE: To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. DESIGN, SETTING, AND PARTICIPANTS: Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. EXPOSURES: Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. MAIN OUTCOME AND MEASURE: Offspring birth weight from 18 studies. RESULTS: Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 x 10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P = 1x10(-5)), respectively. A 1-SD ( approximately 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( approximately 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( approximately 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions. CONCLUSIONS AND RELEVANCE: In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.},
keywords = {birth weight, body mass index, genetics, Mendelian, obesity},
pubstate = {published},
tppubtype = {article}
}