Neuropsychiatric Polygenic Risk Scores Associated With Psychiatric Diagnoses in Veterans

Polygenic risk scores (PRSs) for major depression, schizophrenia, and bipolar disorder were associated with receiving a relevant psychiatric diagnosis and were higher among patients with more hospitalizations, according to a study of US veterans published online in JAMA Psychiatry.

“Using diagnoses confirmed by in-person structured clinical interviews and current neuropsychiatric PRSs, the validity of an electronic health records–based phenotyping approach in US veterans was demonstrated,” researchers wrote, “highlighting the potential of PRSs for disentangling biological and mediated pleiotropy.”

The study included 707,299 patients who use the Veterans Health Administration health care system, including an embedded cohort of 9378 patients with confirmed schizophrenia or bipolar 1 disorder. Researchers compared the performance of schizophrenia, bipolar disorder, and major depression PRSs in participants of African or European ancestry in the Million Veteran Program and explored links between PRSs and more than 1500 disease categories based on billing codes.

Among the 9378 patients with confirmed schizophrenia or bipolar 1 disorder diagnoses, 95.6% were correctly identified using billing codes, according to the study.

In patients of European ancestry, PRSs were robustly associated with having received a diagnosis of schizophrenia (researchers reported a 1.81 odds ratio) or bipolar disorder (1.42 odds ratio). However, in patients of African ancestry, corresponding effect sizes were smaller: odds ratios were 1.35 for having received a diagnosis of schizophrenia and 1.16 for having received a diagnosis of bipolar disorder.

Meanwhile, higher neuropsychiatric PRSs were associated with elevated risk for a range of psychiatric and physical problems, even when patients lacked a formal diagnosis.

“Individual-level PRSs informed by large-scale genetic studies are portable across US health care systems and have emergent potential for risk stratification,” researchers wrote, “albeit with disparate specificity across ancestries.”

Reference

Bigdeli TB, Voloudakis G, Barr PB, et al. Penetrance and pleiotropy of polygenic risk scores for schizophrenia, bipolar disorder, and depression among adults in the US Veterans Affairs health care system. JAMA Psychiatry. Published online September 14, 2022. doi: 10.1001/jamapsychiatry.2022.2742