Association Between Maternal Genome-Wide Polygenic Scores for Psychiatric and Neurodevelopmental Disorders and...

Phenotypic links between psychiatric disorders and adverse perinatal events are increasingly being reported, but the mechanisms remain unclear. In this study, we aimed to assess how polygenic scores (PGSs) for 8 psychiatric conditions influence perinatal risk.

The main analysis included 13,085 mothers and their corresponding birth information. PGSs for psychiatric conditions were estimated using genome-wide association study data (excluding the iPSYCH cohort) via LDpred2 and used as exposures. Ten adverse perinatal events from Danish national registers served as outcomes. Associations were analyzed using logistic or multinomial regression, with false discovery rate correction applied.

We found that PGSs for psychiatric conditions were associated with heavy smoking (attention-deficit/hyperactivity disorder [ADHD], anxiety, and depression), lower likelihood of being overweight/obese (schizophrenia, anorexia nervosa, and obsessive-compulsive disorder [OCD]), very young maternal age (<20 years) at childbirth (ADHD, depression, and anxiety), and non-cohabitation (ADHD, schizophrenia, anxiety, and depression). Little evidence of an association between maternal PGSs for psychiatric conditions and birth weight, gestational age, and labor presentation was identified. We identified a novel dose-response relationship in which higher PGSs for ADHD, anxiety, and depression were associated with a greater cumulative burden of adverse perinatal events, whereas higher PGSs for anorexia nervosa and OCD were linked to a lower burden.

High genetic liability for psychiatric conditions may partially explain the observed phenotypic associations between maternal mental illness and adverse perinatal events, with higher genetic liability generally associated with either an increase or decrease in the cumulative burden of adverse perinatal events in a dose-response-like manner.