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Study Links Maternal Mental Illness-Related Variants to Perinatal Risk Factors For Offspring

NEW YORK – New research suggests that mental health-related variants in mothers-to-be may influence traits, behaviors, or conditions before, during, and after pregnancy that have a bearing on their children's future risk of mental health conditions.

"[O]ur results indicate that genetic risk may account in part for previously identified associations between perinatal factors and offspring mental illness," senior and corresponding author Andrea Roberts, an environmental health researcher at Harvard T.H. Chan School of Public Health, and her colleagues wrote in Science Advances on Wednesday. "These results warrant consideration when evaluating the degree to which interventions to reduce perinatal risk factors will affect offspring mental health."

Starting with data for more than 116,400 female nurses enrolled in the Nurses' Health Study 2 from 1996 to 1999, the researchers identified 13,313 genotyped participants of European ancestry from prior genome-wide association studies, putting together a cross-mental illness polygenic risk score (PRS) as well as PRSs for half a dozen conditions: attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, major depressive disorder (MDD), neuroticism, and schizophrenia.

The team also found that certain sets of PRS tended to overlap with one another, particularly risk scores for ADHD, bipolar disorder, and schizophrenia. High genetic risk of those conditions often coincided with reduced genetic risk of conditions such as neuroticism and MDD, and vice versa. In contrast, ASD genetic risk did not seem to overlap with PRS for any of the other conditions.

From there, the researchers followed more than 19,700 pregnancies in 8,983 women, analyzing maternal variants associated with mental illness in the context of perinatal factors ranging from smoking or alcohol use during pregnancy to pregestational weight, birth weight, or pregnancy factors.

They found that the genetic risk of ADHD and risk of mental illness in general coincided with individuals' likelihood of smoking while pregnant, for example, while the neuroticism PRS showed more tenuous ties to smoking during pregnancy.

Women with higher-than-usual genetic risk of ADHD, depression, or mental illness overall tended to breastfeed for just one month or less, the team reported, and those with bipolar disorder were more apt to use alcohol during pregnancy. Both the bipolar disorder and ADHD genetic scores coincided with pre-pregnancy weight, whereas overall mental health risk and genetic risk of MDD corresponded with intimate partner violence before pregnancy.

On the other hand, the researchers did not see ties between ASD or schizophrenia PRS and perinatal factors. Likewise, their analyses did not point to PRS associations with other pregnancy features such as pregnancy length, pointing to the possibility that the genetic risk scores have a more pronounced influence over perinatal lifestyle, trait, and behavior features for mothers-to-be.

"As PRS were associated only with exposures closely tied to maternal behavior … and not pregnancy length," the authors explained, "these results raise the possibility that maternal genetic loading for mental illness may affect maternal behaviors, which then manifest as perinatal risk factors for offspring, who also inherit maternal genetic risk for mental illness."

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