Polygenic differential susceptibility to prenatal adversity

Abstract

A recent article in this journal reported a number of gene × environment interactions involving a serotonin transporter-gene network polygenic score and a composite index of prenatal adversity predicting several problem behavior outcomes at 48 months (e.g., anxious/depressed, pervasive developmental problems) and at 60 months (e.g., withdrawal, internalizing problems), yet did not illuminate the nature or form these genetic × environment interactions took. Here we report results of six additional analyses to evaluate whether these interactions reflected diathesis-stress or differential-susceptibility related processes. Analyses of the regions of significance and proportion of interaction index are consistent with the diathesis-stress model, seemingly because of the truncated nature of the adversity score (which did not extend to supportive/positive prenatal experiences/exposures); in contrast, the proportion (of cases) affected index favors the differential-susceptibility model. These results suggest the need for future studies to extend measurement of the prenatal environment to highly supportive experiences and exposures.