Prognostic value of polygenic risk scores for adults with psychosis

Isotta Landi, Deepak A. Kaji, Liam Cotter, Tielman Van Vleck, Gillian Belbin, Michael Preuss, Ruth J.F. Loos, Eimear Kenny, Benjamin S. Glicksberg, Noam D. Beckmann, Paul O’Reilly, Eric E. Schadt, Eric D. Achtyes, Peter F. Buckley, Douglas Lehrer, Dolores P. Malaspina, Steven A. McCarroll, Mark H. Rapaport, Ayman H. Fanous, Michele T. PatoCarlos N. Pato, Tim B. Bigdeli, Girish N. Nadkarni, Alexander W. Charney

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Polygenic risk scores (PRS) summarize genetic liability to a disease at the individual level, and the aim is to use them as biomarkers of disease and poor outcomes in real-world clinical practice. To date, few studies have assessed the prognostic value of PRS relative to standards of care. Schizophrenia (SCZ), the archetypal psychotic illness, is an ideal test case for this because the predictive power of the SCZ PRS exceeds that of most other common diseases. Here, we analyzed clinical and genetic data from two multi-ethnic cohorts totaling 8,541 adults with SCZ and related psychotic disorders, to assess whether the SCZ PRS improves the prediction of poor outcomes relative to clinical features captured in a standard psychiatric interview. For all outcomes investigated, the SCZ PRS did not improve the performance of predictive models, an observation that was generally robust to divergent case ascertainment strategies and the ancestral background of the study participants.

Original languageEnglish (US)
Pages (from-to)1576-1581
Number of pages6
JournalNature Medicine
Volume27
Issue number9
DOIs
StatePublished - Sep 2021
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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