Post by Stephanie Williams
What's the science?
Factors that occur before and during pregnancy, including maternal alcohol intake, poor nutrition, and stressful life events, have previously been linked with a higher risk for neurodevelopmental disorders in offspring. Most studies that assess the link between lifestyle factors and neurodevelopmental disorder risk do not properly account for maternal genotype, and could therefore be confounded by the genetics of the mother. This week in Jama JAMA Psychiatry, Leppert and colleagues assess the relationship between maternal lifestyle factors and maternal polygenic risk scores for neurodevelopmental conditions.
How did they do it?
The authors analyzed data collected in an ongoing longitudinal study “Children of the 90s” of a large number (N=7921) of mothers in the United Kingdom. The dataset included genetic data and information on the health and lifestyles of the children and their mothers. Mothers were asked to report their drinking and smoking habits, use of antidepressants, and nutritional supplements. They were assigned a ‘stressful life score’ based on a self-report of whether they had experienced 18 different stressful life events. Analysis of the mother’s blood was used to determine nutritional status and toxin exposure. Obstetric records were used to assess adverse birth events like low birth weight. The authors used previously identified risk alleles to calculate a polygenic risk score, which is a score calculated from the number of variants (single nucleotide polymorphisms) for a gene that indicates a certain amount of genetic risk for a disorder or disease. The authors were interested in investigating whether the polygenic risk scores for 3 different disorders, Attention Deficit Disorder (ADHD), Autism Spectrum Disorder, and Schizophrenia were associated with the lifestyle factors mentioned above. The authors calculated an association score for each of the lifestyle-related variables and the polygenic risk score for the 3 diseases.
What did they find?
The authors identified several associations between lifestyle factors and maternal risk alleles. Specifically, the authors identified associations between genetic risk for ADHD and SCZ and higher risk of smoking, and pregnancy BMI (higher BMI for ADHD, lower BMI for schizophrenia). Genetic risk for ADHD was associated with several additional factors, including infections, use of acetaminophen during late pregnancy, lower blood levels of mercury and higher blood levels of cadmium. The only factors found to be associated with polygenic risk score for all three disorders were maternal stressful life events during pregnancy and a higher risk for experiencing severe depression. Importantly, the authors point out that they found little evidence for associations between genetic risk for autism and schizophrenia and lifestyle factors (except for BMI with schizophrenia).
What's the impact?
This work emphasizes the importance of accounting for maternal genetics when drawing conclusions about lifestyle factors that affect risk for neurodevelopmental disorders. The authors identified for the first time associations between genetic risk for ADHD and several factors, including infections, acetaminophen, and blood levels of toxins. The results of the study could inform the care and treatment of pregnant women carrying risk alleles for neurodevelopmental disorders.
Leppert, B et al. (2019) Association of maternal neurodevelopmental risk alleles with early-life exposures. JAMA Psychiatry. Access the original scientific publication here