Cross‐Ancestry Polygenic Prediction of Bipolar Disorder and Obsessive‐Compulsive Disorder in India

Most genetic studies of psychiatric disorders have been conducted predominantly in populations of European ancestry, limiting evidence for the transferability of polygenic scores (PGS) to other populations. This cross-sectional study evaluated the predictive performance of European-derived PGS for bipolar disorder (BD) and obsessive-compulsive disorder (OCD) in an Indian sample. Participants (N = 2531) included individuals with BD (N = 463), OCD (N = 554), and controls (N = 1514) recruited from hospital- and community-based samples. Genotyping was performed using the Illumina Global Screening Array. PGS were derived from the summary statistics of European-ancestry genome-wide association studies using two Bayesian methods, PRS-CS-auto and SBayesRC. Principal component analyses demonstrated genetic overlap of the study population with other South Asian populations. BD PGS showed significant predictive performance, explaining approximately 6%-7% of liability-scale variance with PGS-only AUCs of ~0.71. OCD PGS showed lower but significant predictive performance, explaining ~2%-3% of variance with AUCs of approximately 0.59. Bayesian approaches showed better predictive performance than conventional clumping-and-thresholding. These findings demonstrate that European-derived psychiatric PGS can retain predictive information in an Indian population, although performance differed between disorders. The application of Bayesian PGS methods in this Indian cohort supports their utility for cross-ancestry prediction, while reinforcing the need for larger genomic studies in South Asian and other underrepresented populations.

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Journal
American Journal of Medical Genetics Part B Neuropsychiatric Genetics
Published
2026-10-27
DOI
https://doi.org/10.1002/ajmg.b.70037
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
0.00

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article

Cross‐Ancestry Polygenic Prediction of Bipolar Disorder and Obsessive‐Compulsive Disorder in India

Bharath Holla, Pavithra Jayasankar, Y.C. Janardhan Reddy, Jayant Mahadevan et al.
5 links
American Journal of Medical Genetics Part B Neuropsychiatric Genetics
Genetic Associations and Epidemiology
article

Cross‐Ancestry Polygenic Prediction of Bipolar Disorder and Obsessive‐Compulsive Disorder in India

Bharath Holla, Pavithra Jayasankar, Y.C. Janardhan Reddy, Jayant Mahadevan, Sanjeev Jain, Swarna Buddha Nayok, Nora I. Strom, Biju Viswanath, Reeteka Sud, Patrick F. Sullivan, Srinivas Balachander, Peter P. Zandi, Vivek Benegal, Suhas Ganesh, Meghana Janardhanan, Meera Purushottam, Manuel Mattheisen, Hailiang Huang
article en

Abstract

Most genetic studies of psychiatric disorders have been conducted predominantly in populations of European ancestry, limiting evidence for the transferability of polygenic scores (PGS) to other populations. This cross-sectional study evaluated the predictive performance of European-derived PGS for bipolar disorder (BD) and obsessive-compulsive disorder (OCD) in an Indian sample. Participants (N = 2531) included individuals with BD (N = 463), OCD (N = 554), and controls (N = 1514) recruited from hospital- and community-based samples. Genotyping was performed using the Illumina Global Screening Array. PGS were derived from the summary statistics of European-ancestry genome-wide association studies using two Bayesian methods, PRS-CS-auto and SBayesRC. Principal component analyses demonstrated genetic overlap of the study population with other South Asian populations. BD PGS showed significant predictive performance, explaining approximately 6%-7% of liability-scale variance with PGS-only AUCs of ~0.71. OCD PGS showed lower but significant predictive performance, explaining ~2%-3% of variance with AUCs of approximately 0.59. Bayesian approaches showed better predictive performance than conventional clumping-and-thresholding. These findings demonstrate that European-derived psychiatric PGS can retain predictive information in an Indian population, although performance differed between disorders. The application of Bayesian PGS methods in this Indian cohort supports their utility for cross-ancestry prediction, while reinforcing the need for larger genomic studies in South Asian and other underrepresented populations.

American Journal of Medical Genetics Part B Neuropsychiatric Genetics
Broad Institute (US), University of North Carolina at Chapel Hill (US), University of Bern (CH), Dalhousie University (CA), Harvard University (US), Johns Hopkins University (US), Aarhus University (DK), Johns Hopkins Medicine (US), Stockholm County Council (SE), Karolinska Institutet (SE), LMU Klinikum (DE), Massachusetts General Hospital (US), Universitätsklinikum Würzburg (DE), Stockholm Health Care Services (SE), Stanley Center for Psychiatric Research (US), Institut für Psychiatrische Phänomik und Genomik (DE), National Institute of Mental Health and Neurosciences (IN), Ludwig-Maximilians-Universität München (DE)
Wellcome Trust, Department of Biotechnology, Ministry of Science and Technology, India, Indian Council of Medical Research, The Wellcome Trust DBT India Alliance, Medical Research Council
Good health and well-being
Openalex Percentile: Top 14%
Genetic Associations and Epidemiology
DOIOpen Access PDFOpenAlex
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