Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 73,307 bioRxiv papers from 319,075 authors.

Penetrance and pleiotropy of polygenic risk scores for schizophrenia in 106,160 patients across four healthcare systems

By Amanda B Zheutlin, Jessica Dennis, Richard Karlsson Linnér, Arden Moscati, Nicole Restrepo, Peter Straub, Douglas Ruderfer, Victor M Castro, Chia-Yen Chen, Tian Ge, Laura M Huckins, Alexander Charney, H Lester Kirchner, Eli A Stahl, Christopher F Chabris, Lea K Davis, Jordan W Smoller

Posted 18 Sep 2018
bioRxiv DOI: 10.1101/421164

OBJECTIVE: Individuals at high risk for schizophrenia may benefit from early intervention but few validated risk predictors are available. Genetic profiling is one approach to risk stratification that has been extensively validated in research cohorts, but its utility in clinical settings remains largely unexplored. Moreover, the broad health consequences of a high genetic risk of schizophrenia are poorly understood, despite being relevant to treatment decisions. METHOD: We used electronic health records for 106,160 patients from four healthcare systems to evaluate the penetrance and pleiotropy of genetic risk for schizophrenia. Polygenic risk scores (PRSs) for schizophrenia were calculated from summary statistics and tested for association with 1359 disease categories, including schizophrenia and psychosis, in phenome-wide association studies. Effects were combined through meta-analysis across sites. RESULTS: PRSs were robustly associated with schizophrenia (odds ratio per standard deviation increase in PRS=1.55 [95% confidence interval (CI), 1.4-1.7], p=4.48 x 10-16) and patients in the highest risk decile of the PRS distribution had up to 4.6-fold increased odds of schizophrenia compared to those in the bottom decile (95% CI, 2.9-7.3, p=1.37 x 10-10). PRSs were also positively associated with a range of other phenotypes, including anxiety, mood, substance use, neurological, and personality disorders, as well as suicidal behavior, memory loss, and urinary syndromes; they were inversely related to obesity. CONCLUSIONS: We demonstrate that an available measure of genetic risk for schizophrenia is robustly associated with schizophrenia in healthcare settings and has pleiotropic effects on related psychiatric disorders as well as other medical syndromes. Our results provide an initial indication of the opportunities and limitations that may arise with the future application of PRS testing in healthcare systems.

Download data

  • Downloaded 1,249 times
  • Download rankings, all-time:
    • Site-wide: 5,973 out of 73,307
    • In genetics: 466 out of 4,027
  • Year to date:
    • Site-wide: 11,399 out of 73,307
  • Since beginning of last month:
    • Site-wide: 11,399 out of 73,307

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News