Candidate Gene–Environment Interaction Research

Abstract

Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing our understanding of the development of psychopathology. It represents a clear theoretical advance over studying these factors in isolation. However, research at the intersection of multiple fields creates many challenges. We review several reasons why the rapidly expanding candidate gene-environment interaction (cGxE) literature should be considered with a degree of caution. We discuss lessons learned about candidate gene main effects from the evolving genetics literature and how these inform the study of cGxE. We review the importance of the measurement of the gene and environment of interest in cGxE studies. We discuss statistical concerns with modeling cGxE that are frequently overlooked. And we review other challenges that have likely contributed to the cGxE literature being difficult to interpret, including low power and publication bias. Many of these issues are similar to other concerns about research integrity (e.g., high false positive rates) that have received increasing attention in the social sciences. We provide recommendations for rigorous research practices for cGxE studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes.

ALDH2*2 and peer drinking in East Asian college students

“…We selected a genetic marker ( ALDH2 rs671) and environmental effect (a measure of peer alcohol use) with strong empirical evidence and, respectively, biological and theoretical relevance (39). In our analyses we attempted to rule out potential confounders, including by controlling for all relevant gene × covariate and environment × covariate interactions (30) and by testing for gene–environment correlation (rGE) (39). Similar to the Irons et al (18) study, we found no rGE between ALDH2 *2 status and our measure of the peer environment.…”

Serotonin transporter polymorphism moderates the effects of caregiver intrusiveness on ADHD symptoms among institutionalized preschoolers

“…The sample is small, and, thus, this study is limited in its statistical power [68], which might have contributed to some (or all) of the null results reported and discussed, and to the small amount of variance accounted by the two-way interaction involving 5-HTTLPR and intrusiveness. In consequence, interpretation and generalization of the results must be made carefully, and replication in larger samples of institutionally reared children is warranted.…”

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

“…First, statistical analysis for the main effect of the CNR1 SNPs and the CNR1 SNPs × RLE interactions on possible migraine and migraine‐related symptoms were carried out in the total sample, according to a recent guideline (Dick et al 2015). Pairwise deletion was used to handle missing data.…”