Polygenic prediction of the risk of perinatal depressive symptoms.

Polina Girchenko,Ville Rantalainen,Katri Räikkönen,Tuomas Kvist,Jari Lahti,Marius Lahti‐Pulkkinen,Eero Kajantie,Hannele Laivuori,Elisabeth B. Binder,Darina Czamara,Pia M. Villa,Esa Hämäläinen

doi:10.1002/da.23066

Abstract

Perinatal depression carries adverse effects on maternal health and child development, but genetic underpinnings remain unclear. We investigated the polygenic risk of perinatal depressive symptoms. About 742 women from the prospectivePrediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction cohort were genotyped and completed the Center for Epidemiologic Studies Depression scale 14 times during the prenatal period and twice up to 12 months postpartum. Polygenic risk scores for major depressive disorder, bipolar disorder, schizophrenia, and cross-disorder were calculated using multiple p-value thresholds. Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder, but not bipolar disorder, were associated with higher prenatal and postpartum depressive symptoms (0.8%-1% increase per one standard deviation increase in polygenic risk scores). Prenatal depressive symptoms accounted for and mediated the associations between the polygenic risk scores and postpartum depressive symptoms (effect size proportions-mediated: 52.2%-88.0%). Further, the polygenic risk scores were associated with 1.24-1.45-fold odds to belong to the group displaying consistently high compared with consistently low depressive symptoms through out the prenatal and postpartum periods. Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder in non-perinatal populations generalize to perinatal depressive symptoms and may afford to identify women for timely preventive interventions.

Highlights

Maternal perinatal depression, defined as depression during pregnancy or within 12 months of childbirth, affects over 1 of 10 women in childbearing age (World Health Organizaton, 2015)
To study if the polygenic risk score (PRS) were associated with fluctuating or persistently high levels of prenatal and postpartum depressive symptoms, we first applied latent class analysis (LCA) to identify subgroups of women based on their depressive symptoms levels across all measurements
We found that the PRSs for major depressive disorder (MDD2018), major depressive disorder (MDD2019), SCZ2014, and SCZ2018 and CD, but not bipolar disorder (BD2018) or bipolar disorder (BD2019), predicted higher levels of prenatal and postpartum depressive symptoms

Summary

Introduction

Maternal perinatal depression, defined as depression during pregnancy or within 12 months of childbirth, affects over 1 of 10 women in childbearing age (World Health Organizaton, 2015). Reported clinically relevant symptoms are even more common, affecting 1 of 5 women (Kumpulainen et al, 2018; Lahti et al, 2017) It causes a major burden on the health and well‐being of the women and is associated with problems such as gestational diabetes and hypertension in pregnancy (Bansil et al, 2009) and obesity (Kumpulainen et al, 2018). The polygenic risk scores were associated with 1.24–1.45‐fold odds to belong to the

Methods

Results

Discussion

Conclusion