Pervasive Modulation of Obesity Risk by the Environment and Genomic Background

• Main Authors: Sini Nagpal, Greg Gibson, Urko M. Marigorta
• Format: Article
• Language: English
• Published: MDPI AG 2018-08-01
• Series: Genes
• Subjects: diseases of affluence; body mass index; gene-by-environment interactions; genome-wide association studies (GWAS); polygenic scores (PGS); epistasis; allele expressivity; UK Biobank
• Online Access: http://www.mdpi.com/2073-4425/9/8/411

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).