Gene-environment interactions and obesity - Further aspects of genomewide association studies

Advances in genotyping technologies have facilitated the advent of the genomewide association studies in large study populations and thereby led to the identification of an impressive-and still increasing-number of genetic variants with significant impact on the risk of widespread lifestyle health problems such as obesity, diabetes, and cardiovascular disease. Yet, the scientific community is a long way from reaching a comprehensive picture of the heritable components of these diseases and advancing from plain statistical significance into a biological understanding where the true contribution to a trait is recognized. Increasingly large study populations, denser single-nucleotide polymorphism mapping, deep sequencing, and raised awareness of the importance of structural variants may add to the known genetic variance underlying common complex disorders; however, genetic variance alone probably cannot account for disease susceptibility without the addition of pre- and postnatal environmental and/or behavioral factors. Moreover, an interaction between genetic and environmental factors may hinder the detection of genetic effects if not accounted for, e.g., in genomewide association studies, and prospective cohort studies have hence been proposed to surpass the classic case-control design. With a focus on obesity we describe some of the recently reported gene-environment interactions for polymorphisms identified in the FTO and INSIG2 genes. Ultimately, a thorough understanding of the gene-environment interactions underlying a common complex condition such as obesity may suggest novel treatment or intervention strategies to complement the harmful effect of detrimental genetic variation and thus may assist in improving the quality of life for affected individuals. (C) 2009 Elsevier Inc. All rights reserved.