Placental genomic risk scores and early neurodevelopmental outcomes

Gianluca Ursini, Giovanna Punzi, Benjamin W. Langworthy, Qiang Chen, Kai Xia, Emil A. Cornea, Barbara D. Goldman, Martin A. Styner, Rebecca C. Knickmeyer, John H. Gilmore, Daniel R. Weinberger

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Tracing the early paths leading to developmental disorders is critical for prevention. In previous work, we detected an interaction between genomic risk scores for schizophrenia (GRSs) and early-life complications (ELCs), so that the liability of the disorder explained by genomic risk was higher in the presence of a history of ELCs, compared with its absence. This interaction was specifically driven by loci harboring genes highly expressed in placentae from normal and complicated pregnancies [G. Ursini et al., Nat. Med. 24, 792–801 (2018)]. Here, we analyze whether fractionated genomic risk scores for schizophrenia and other developmental disorders and traits, based on placental gene-expression loci (PlacGRSs), are linked with early neurodevelopmental outcomes in individuals with a history of ELCs. We found that schizophrenia’s PlacGRSs are negatively associated with neonatal brain volume in singletons and offspring of multiple pregnancies and, in singletons, with cognitive development at 1 y and, less strongly, at 2 y, when cognitive scores become more sensitive to other factors. These negative associations are stronger in males, found only with GRSs fractionated by placental gene expression, and not found in PlacGRSs for other developmental disorders and traits. The relationship of PlacGRSs with brain volume persists as an anlage of placenta biology in adults with schizophrenia, again selectively in males. Higher placental genomic risk for schizophrenia, in the presence of ELCs and particularly in males, alters early brain growth and function, defining a potentially reversible neurodevelopmen.

Original languageEnglish (US)
Article numbere2019789118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 16 2021


  • Schizophrenia | developmental trajectories

ASJC Scopus subject areas

  • General


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