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Genes 2018, 9(8), 411; https://doi.org/10.3390/genes9080411

Pervasive Modulation of Obesity Risk by the Environment and Genomic Background

Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, GA 30332, USA
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Received: 1 June 2018 / Revised: 30 July 2018 / Accepted: 30 July 2018 / Published: 14 August 2018
(This article belongs to the Special Issue Evolutionary Medicine)
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Abstract

The prevalence of the so-called diseases of affluence, such as type 2 diabetes or hypertension, has increased dramatically in the last two generations. Although genome-wide association studies (GWAS) have discovered hundreds of genes involved in disease etiology, the sudden increase in disease incidence suggests a major role for environmental risk factors. Obesity constitutes a case example of a modern trait shaped by contemporary environment, although with considerable debates about the extent to which gene-by-environment (G×E) interactions accentuate obesity risk in individuals following obesogenic lifestyles. Although interaction effects have been robustly confirmed at the FTO locus, accumulating evidence at the genome-wide level implicates a role for polygenic risk-by-environment interactions. Through a variety of analyses using the UK Biobank, we confirm that the genomic background plays a major role in shaping the expressivity of alleles that increase body mass index (BMI). View Full-Text
Keywords: diseases of affluence; body mass index; gene-by-environment interactions; genome-wide association studies (GWAS); polygenic scores (PGS); epistasis; allele expressivity; UK Biobank diseases of affluence; body mass index; gene-by-environment interactions; genome-wide association studies (GWAS); polygenic scores (PGS); epistasis; allele expressivity; UK Biobank
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Nagpal, S.; Gibson, G.; Marigorta, U.M. Pervasive Modulation of Obesity Risk by the Environment and Genomic Background. Genes 2018, 9, 411.

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