Genetic Liability for ADHD, Schizophrenia, Increase Risk for Pregnancy-Related Factors

Genetic liability for neurodevelopmental conditions increased the risk for many pregnancy-related factors, according to study results published in JAMA Psychiatry.

Investigators from the Norwegian Institute of Public Health sourced data from the Norwegian Mother, Father and Child Cohort Study (MoBa) which was a population-based pregnancy cohort study conducted between 1999 and 2008. Mothers (n=14,539) and fathers (n=14,897) gave blood samples to evaluate polygenetic scores (PGS) for attention-deficit/hyperactivity disorder (ADHD), autism, and schizophrenia. Genetic liabilities for neurodevelopmental conditions were related with pregnancy-related measures.

Maternal PGS for ADHD was significantly associated with 17 behavior and lifestyle characteristics, metabolic features, infectious and autoimmune diseases, indications for medicine use, and other physical health conditions related with pregnancy. The most significant associations were cigarette smoking (odds ratio [OR], 1.26; P =2.2´10^–14), prepregnancy BMI (OR, 0.25; P =7.88´10^–13), lifetime depression (OR, 1.12; P =3.73´10^–9), maternal age (OR, -0.21; P =6.18´10^–9), depression or anxiety symptoms (OR, 1.15; P =5.48´10^–7), not taking supplements (OR, 1.09; P =7.04´10^–5), weight gain (OR, 0.20; P =9.63´10^–5), folate supplementation during pregnancy (OR, 0.92; P =3.23´10^–4), and asthma (OR, 1.15; P =8.59´10^–4).

For autism maternal PGS, there were seven significant associations, with lifetime depression (OR, 1.12; P =9.70´10^–9) and depression or anxiety symptoms (OR, 1.13; P =3.62´10^–5) as the most significant.

Schizophrenia PGS in mothers was associated with 11 pregnancy-related factors, particularly lifetime depression (OR, 1.16; P =3.11´10^–13), prepregnancy BMI (OR, -0.18; P =2.26´10^–7), coffee consumption (OR, 1.09; P =8.92´10^–7), depression or anxiety symptoms (OR, 1.13; P =1.71´10^–5), depression or anxiety medication use (OR, 1.37; P =3.72´10^–5), depression medication use (OR, 1.43; P =2.76´10^–5), and cigarette smoking (OR, 1.12; P =1.10´10^–4).

A subset of 16 pregnancy-related exposures were evaluated among the fathers during the pregnancy. There were two factors which had nonoverlapping associations. Maternal ADHD PGS increased risk for maternal smoking in pregnancy and maternal schizophrenia PGS increased risk for maternal coffee consumption during pregnancy. Neither of these associations were significant for the fathers.

Results from sensitivity analyses which used inverse probability weighing and multiple imputation had similar findings as the main analysis.

The major limitation of this study was the small effect sizes for autism due to low common genetic heritability of ASD.

The study authors concluded, “Our study demonstrates associations of ADHD genetic liability with several pregnancy-related factors that have been considered predisposing factors for offspring ADHD. Schizophrenia genetic liability also showed associations with some pregnancy-related factors, including lower prepregnancy BMI, higher pregnancy weight gain, and increased smoking during pregnancy. Autism genetic liability showed few associations with pregnancy-related factors beyond depression. Our findings suggest that pregnant individuals with high ADHD or schizophrenia genetic liability are at increased risk of adverse pregnancy-related exposures.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Havdahl A, Wootton RE, Leppert B, et al. Associations between pregnancy-related predisposing factors for offspring neurodevelopmental conditions and parental genetic liability to attention-deficit/hyperactivity disorder, autism, and schizophrenia: The Norwegian Mother, Father and Child Cohort Study (MoBa). JAMA Psychiatry. Published online July 6, 2022. doi:10.1001/jamapsychiatry.2022.1728