Road to Unravel Gene–Environment Interactions on Cardiovascular Complex Diseases

See Article by Hindy et al Genome-wide association studies have contributed to the identification of genetic variants associated with coronary artery disease (CAD); a recent genome-wide association studies meta-analysis reported 66 loci significantly associated with CAD.1 However, the heritability explained by these loci remains low, around 15%. One of the limitations of genome-wide association studies is the likelihood of false-negative results related to the strict and commonly defined genome-wide significance threshold that accounts for multiple comparisons using the Bonferroni correction ( P value <5×10−8). Other methods to correct for the high number of comparisons, such as false discovery rate, provide a larger number of associated loci, but the explained heritability remains around 21%.2 The debate about the role of genetics (nature) versus the role of environmental factors (nurture) on health has classically confronted and opposed these 2 influences, but the interplay between the 2 also contributes to the pathogenesis of complex diseases and could partially explain the missing heritability of CAD. The gene–environment interaction (G×E) adds complexity to the already complex individual roles of genes and environment in the pathogenesis of some diseases, such as CAD. There are several reasons to study G×E interactions: helping to unravel the pathogenic mechanisms of a disease such as in phenylketonuria (ie, 2 necessary causes)3 but also in complex diseases4; from a public health perspective, identifying the subset of individuals in whom a preventive intervention …