An Updated Polygenic Index Repository: Expanded Phenotypes, New Cohorts, and Improved Causal Inference
Year: 2025
Type: preprint
Abstract: Polygenic indexes (PGIs) — DNA-based predictors of individual phenotypes — have become essential tools across biomedical and social sciences. We introduce Version 2 of the Polygenic Index Repository, which expands phenotype coverage from 47 to 61, increases the number of participating datasets from 11 to 20, and adopts a more consistent and improved methodology for PGI construction. For 16 phenotypes, we leverage summary statistics from an updated GWAS meta-analysis with greater statistical power compared to the original release, thereby improving the PGI’s predictive power. To improve power for family-based analyses, we provide imputed parental PGIs in all datasets with first-degree relatives and offer a framework for interpreting results from analyses that control for parental PGIs. We illustrate the utility of parental PGIs using two applications: (1) comparing PGI associations with and without parental PGI controls for all phenotypes in two Repository datasets with family data, and (2) for BMI and diastolic blood pressure, exploring the contribution of causal versus non-causal components of PGI associations to the imperfect portability of PGIs across subgroups within a genetic ancestry. Collectively, the updates enhance predictive performance, broaden the Repository’s scope, and introduce novel resources that reduce confounding bias and improve interpretability.
Authors: Robel Alemu, Anastasia Terskaya, Matthew Howell, Junming Guan, Harry Sands, Aaron Kleinman, David Bann, Tim Morris, George B. Ploubidis, Emla Fitzsimons, Kathleen Mullan Harris, Avshalom Caspi, David L. Corcoran, Terrie E. Moffitt, Richie Poulton, Karen Sugden, Benjamin S. Williams, Andrew Steptoe, Olesya Ajnakina, Uku Vainik, Tõnu Esko, Archie Campbell, Caroline Hayward, William G. Iacono, Matt McGue, Robert F. Krueger, Anna R. Docherty, Andrey A. Shabalin, Ralph Hertwig, Philipp Koellinger, David Richter, Jan Goebel, Rafael Ahlskog, Sven Oskarsson, Patrik K.E. Magnusson, K. Paige Harden, Elliot M. Tucker-Drob, Charlotte K. L. Pahnke, Carlo Maj, Frank M. Spinath, Pamela Herd, Jeremy Freese, David Laibson, Michelle N. Meyer, Jonathan Jala, David Cesarini, Alexander Strudwick Young, Patrick Turley, Daniel J. Benjamin, Aysu Okbay
Institutions: Broad Institute, University of California, Los Angeles, The University of Adelaide, Barcelona Institute of Economics, Universitat de Barcelona, Bucknell University, 23andMe (United States), University College London, University of North Carolina at Chapel Hill, Duke University, King's College London, University of Otago, McGill University, University of Tartu, Western General Hospital, Institute of Genetics and Cancer, University of Edinburgh, MRC Human Genetics Unit, University of Minnesota, University of Utah, Max Planck Institute for Human Development, DeSci Foundation, Vrije Universiteit Amsterdam, Freie Universität Berlin, German Institute for Economic Research, Uppsala University, Karolinska Institutet, The University of Texas at Austin, University of Bonn, University Hospital Bonn, Saarland University, Georgetown University, Stanford University, National Bureau of Economic Research, Harvard University, Geisinger Medical Center, Geisinger Health System, New York University, University of Southern California, Amsterdam University Medical Centers
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Beyond Nature vs. Nurture: gene-environment interaction and political behavior, Infrastructure and Core Activities of the Social Science Genetic Association Consortium, Sytematic phenome-wide search for genetic modulators in health and disease, Genome-wide analysis of late-onset Alzheimer's disease using intergenerational, multi-trait, and cross-ancestry data, Genomics and life paths: Unraveling the genetic and social interactions shaping social, economic and health inequalities, Exploiting genomic lottery to understand causality between personality traits, cognition, and health, Genome-Wide Analyses of Health and Well-Being Phenotypes, Studying the Genetics of Aging, Behavioral, and Social Phenotypes in Diverse Populations, Antecedents of Adult Physical Health and Cognitive Risks for Alzheimer's Disease and Related Dementias (ADRD) in Adolescent Family Experiences: A Prospective, Longitudinal Adoption Study, The impact of adverse interpersonal experiences (AIE) on mild cognitive impairment (MCI) and risk for Alzheimer's disease and related dementias (ADRD) in ethnically diverse twins, Mendelian imputation for family-based GWAS and association-by-proxy in diverse ancestries, Integrative Pathways to Health and Illness
OpenAlex ID: W4410477978