ArticleBiological psychiatry2025
Low Stability and Specificity of Polygenic Risk Scores for Major Psychiatric Disorders Limit Their Clinical Utility.
Article in Biological psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Polygenic risk score for neurodevelopmental disorders and cognitive impairment at long-term follow-up of first-episode psychosis.European archives of psychiatry and clinical neuroscience · 2026Article
- Can We Improve the Prediction of Early Onset Mania and Hypomania in the Community?Bipolar disorders · 2026Article
- Beyond DSM Categories: Criteria for Biologically Valid Disease Axes in Psychiatry.Journal of clinical medicine · 2026Review
- Common and rare genetic variants explain distinct diagnostic variance in pediatric attention deficit hyperactivity disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundThere has been little examination of the stability and validity of polygenic risk scores (PRSs), i.e., whether individuals identified as high risk for a disorder with one PRS are identified as high risk with another PRS and whether high-risk individuals have the disorder.
methodsThe UK Biobank recruited 502,534 individuals ages 37 to 73 years in the United Kingdom between 2006 and 2010. PRSs were calculated for 408,853 White British individuals. PRS continuous shrinkage (CS), which uses single nucleotide polymorphism effect sizes under CS, was used to calculate 3 different PRSs for major depressive disorder (MDD), alcohol use disorder (AUD), and type 2 diabetes (T2D) and 2 different PRSs for schizophrenia (SCZ). PRS stability was measured using correlations between different PRSs for the same disorder and the percentage of individuals consistently identified as high risk (top 5% PRS). Sensitivity and specificity were used to measure PRS validity.
resultsCorrelations between PRSs ranged from low to high (SCZ: r = 0.78; MDD: rs = 0.16-0.78; AUD: rs = 0.13-0.90; T2D rs = 0.29-0.77). The percentage of individuals consistently identified as high risk (top 5% PRS) for SCZ with a different SCZ PRS was 47.7%, i.e., less than half of individuals identified as high risk with one PRS were identified as high risk with another PRS. Percentages of individuals consistently identified as high risk were 9.5% to 47.0% for MDD, 8.3% to 63.5% for AUD, and 14.1% to 45.2% for T2D. PRS sensitivity was moderate for MDD (66.1%-74.4%) and AUD (72.3%-74.2%), moderate/good for T2D (77.3%-96.3%), and good for SCZ (90.2%-93.3%). Specificity was low for all PRSs (50.7%-56.4%).
conclusionsLimited stability and specificity of PRSs highlight their current lack of clinical utility in psychiatry.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.