Gene-environment interaction using polygenic scores: Do polygenic scores for psychopathology moderate predictions from environmental risk to behavior problems?

Abstract

The DNA revolution has energized research on interactions between genes and environments (GxE) by creating indices of G (polygenic scores) that are powerful predictors of behavioral traits. Here, we test the extent to which polygenic scores for attention-deficit/hyperactivity disorder and neuroticism moderate associations between parent reports of their children's environmental risk (E) at ages 3 and 4 and teacher ratings of behavior problems (hyperactivity/inattention, conduct problems, emotional symptoms, and peer relationship problems) at ages 7, 9 and 12. The sampling frame included up to 6687 twins from the Twins Early Development Study. Our analyses focused on relative effect sizes of G, E and GxE in predicting behavior problems. G, E and GxE predicted up to 2%, 2% and 0.4%, respectively, of the variance in externalizing behavior problems (hyperactivity/inattention and conduct problems) across ages 7, 9 and 12, with no clear developmental trends. G and E predictions of emotional symptoms and peer relationship problems were weaker. A quarter (12 of 48) of our tests of GxE were nominally significant (p = .05). Increasing the predictive power of G and E would enhance the search for GxE.

Keywords: behavior problems; genotype–environment interaction; polygenic scores; twins.

Figure 1

A 2x2 illustration of the prediction of children’s behavior problems from environments (low vs high risk), from a genetic estimate (low vs high risk), and from their interaction (GxE). See text for explanation.

Figure 2

Variance explained by G (ADHD and neuroticism GPS) and E (environmental risk and discipline factors) predicting teacher-rated hyperactivity/inattention (A), conduct problems (B), emotional symptoms (C) and peer relationship problems (D) at ages 7, 9 and 12.

Figure 3

G+E and GxE prediction of teacher-rated hyperactivity/inattention (A), conduct problems (B), emotional symptoms (C) and peer relationship problems (D) at ages 7, 9 and 12.

Figure 4

Significant GxE interactions in 2x2 analyses of extreme (+/- 1 SD) ADHD GPS, neuroticism GPS and environmental factor scores. Solid line = +1 SD for GPS; dashed line = - 1 SD for GPS.