​Due to the duality of possible effects, the potential benefits of a ketogenic diet in pregnancy should be considered carefully.

​ Moreover, there is a need for more human studies determining the safety of the ketogenic diet for both the fetus and the mother.

​Abstract

​Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories.

Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes.

We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits.

The analyses in the whole sample and stratifying by sex ultimately highlight 139 placenta and schizophrenia-specific risk genes, many being sex-biased; the candidate molecular mechanisms converge on the nutrient-sensing capabilities of placenta and trophoblast invasiveness.

These genes also implicate the Coronavirus-pathogenesis pathway and showed increased expression in placentae from a small sample of SARS-CoV-2-positive pregnancies.

Investigating placental risk genes for schizophrenia and candidate mechanisms may lead to opportunities for prevention that would not be suggested by study of the brain alone.