4.8 Article

Prognostic value of polygenic risk scores for adults with psychosis

期刊

NATURE MEDICINE
卷 27, 期 9, 页码 1576-+

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NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01475-7

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资金

  1. National Institute of Mental Health (NIMH) [R01 MH121923]
  2. NIMH [R01 MH085548, R01 MH104964, R01 MH123451-01]
  3. NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation

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Including polygenic risk scores does not enhance the performance of standard-of-care predictive models for disease outcomes in patients with psychosis, according to research analyzing clinical and genetic data from two multi-ethnic cohorts.
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. The inclusion of polygenic risk scores does not improve the performance of standard-of-care predictive models of disease outcomes in patients with psychosis.

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