Jessica Tyrrell, ; Frayling, Timothy M Gene–obesogenic environment interactions in the UK Biobank study Journal Article In: International Journal of Epidemiology, 2017, (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*
). Abstract | Links | BibTeX | Tags: body mass index, featured, gene–environment, obesogenic environment, social deprivation @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}
}
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.
|
Hill W. D. Hagenaars, Marioni Harris Liewald Davies Okbay McIntosh Gale Deary S P R E S E D C G A A M C R I J Molecular Genetic Contributions to Social Deprivation and Household Income in UK Biobank Journal Article In: Curr Biology, 2016. Abstract | Links | BibTeX | Tags: genetics, GWAS, income, social deprivation, socioeconomic status @article{HillWD2016,
title = {Molecular Genetic Contributions to Social Deprivation and Household Income in UK Biobank},
author = {Hill, W. D.
Hagenaars, S. P.
Marioni, R. E.
Harris, S. E.
Liewald, D. C.
Davies, G.
Okbay, A.
McIntosh, A. M.
Gale, C. R.
Deary, I. J.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27818178},
year = {2016},
date = {2016-11-03},
journal = {Curr Biology},
abstract = {Individuals with lower socio-economic status (SES) are at increased risk of physical and mental illnesses and tend to die at an earlier age [1-3]. Explanations for the association between SES and health typically focus on factors that are environmental in origin [4]. However, common SNPs have been found collectively to explain around 18% of the phenotypic variance of an area-based social deprivation measure of SES [5]. Molecular genetic studies have also shown that common physical and psychiatric diseases are partly heritable [6]. It is possible that phenotypic associations between SES and health arise partly due to a shared genetic etiology. We conducted a genome-wide association study (GWAS) on social deprivation and on household income using 112,151 participants of UK Biobank. We find that common SNPs explain 21% of the variation in social deprivation and 11% of household income. Two independent loci attained genome-wide significance for household income, with the most significant SNP in each of these loci being rs187848990 on chromosome 2 and rs8100891 on chromosome 19. Genes in the regions of these SNPs have been associated with intellectual disabilities, schizophrenia, and synaptic plasticity. Extensive genetic correlations were found between both measures of SES and illnesses, anthropometric variables, psychiatric disorders, and cognitive ability. These findings suggest that some SNPs associated with SES are involved in the brain and central nervous system. The genetic associations with SES obviously do not reflect direct causal effects and are probably mediated via other partly heritable variables, including cognitive ability, personality, and health.},
keywords = {genetics, GWAS, income, social deprivation, socioeconomic status},
pubstate = {published},
tppubtype = {article}
}
Individuals with lower socio-economic status (SES) are at increased risk of physical and mental illnesses and tend to die at an earlier age [1-3]. Explanations for the association between SES and health typically focus on factors that are environmental in origin [4]. However, common SNPs have been found collectively to explain around 18% of the phenotypic variance of an area-based social deprivation measure of SES [5]. Molecular genetic studies have also shown that common physical and psychiatric diseases are partly heritable [6]. It is possible that phenotypic associations between SES and health arise partly due to a shared genetic etiology. We conducted a genome-wide association study (GWAS) on social deprivation and on household income using 112,151 participants of UK Biobank. We find that common SNPs explain 21% of the variation in social deprivation and 11% of household income. Two independent loci attained genome-wide significance for household income, with the most significant SNP in each of these loci being rs187848990 on chromosome 2 and rs8100891 on chromosome 19. Genes in the regions of these SNPs have been associated with intellectual disabilities, schizophrenia, and synaptic plasticity. Extensive genetic correlations were found between both measures of SES and illnesses, anthropometric variables, psychiatric disorders, and cognitive ability. These findings suggest that some SNPs associated with SES are involved in the brain and central nervous system. The genetic associations with SES obviously do not reflect direct causal effects and are probably mediated via other partly heritable variables, including cognitive ability, personality, and health. |
