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Genes found in placenta may affect schizophrenia risk

Research findings published in Nature Medicine showed the most significant genetic variants linked to schizophrenia converge in the placenta; however, only certain variations in the genetic make-up may result in schizophrenia when there are complications during pregnancy.

These variants affect the placental response to stress from its environment, according to the study.

"For the first time, we have found an explanation for the connection between early life complications, genetic risk and their impact on mental illness, and it all converges on the placenta," Daniel R. Weinberger, MD, of the Lieber Institute for Brain Development and the department of psychiatry and behavioral sciences at Johns Hopkins University Medical School, said in a press release.

To determine the environmental context in which genes alter schizophrenia susceptibility, researchers performed a genome-wide association study to obtain polygenic risk scores (PRSs) in independent samples of more than 2,800 adults (2,038 with schizophrenia) from the U.S., Italy and Germany. According to the press release, all participants underwent genetic testing and surveying for obstetrical history information.

The researchers found the intra-uterine environment affects the association between schizophrenia and genomic risk. Analysis revealed a prominent interaction between genes linked to schizophrenia risk and history of potentially serious pregnancy complications. Participants at high genetic risk with early life complications had more than a fivefold greater likelihood of developing schizophrenia compared with those with similar high genetic risk but without history of serious obstetrical complications, according to the press release.

In addition, researchers performed a series of analyses on gene expression in multiple placenta tissue samples, including those from pregnancies with complications — preeclampsia, intrauterine growth restriction, etc. — according to the release. They found the genes driving the interaction between polygenic risk score and early life complications were involved in cellular stress response.

“Our results underscore the importance of assessing early environmental factors such as obstetrical complications, in addition to genetic risk, to fully investigate their joint effect on susceptibility to neurodevelopmental disorders,” Weinberger and colleagues wrote. “Our results also point to the placenta as a crucial mediator of this interaction in relation to schizophrenia in particular, but likely to other neurodevelopmental disorders in general, underscoring the need for further research on placenta physiology in the context of brain development and genomic risk.” – by Savannah Demko

Disclosures: The authors report no relevant financial disclosures.