npj Genomic Medicine (Feb 2025)
Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height
- A. Papadopoulou,
- E. M. Litkowski,
- M. Graff,
- Z. Wang,
- R. A. J. Smit,
- G. Chittoor,
- I. Dinsmore,
- N. S. Josyula,
- M. Lin,
- J. Shortt,
- W. Zhu,
- S. L. Vedantam,
- L. Yengo,
- A. R. Wood,
- S. I. Berndt,
- I. A. Holm,
- F. D. Mentch,
- H. Hakonarson,
- K. Kiryluk,
- C. Weng,
- G. P. Jarvik,
- D. Crosslin,
- D. Carrell,
- I. J. Kullo,
- O. Dikilitas,
- M. G. Hayes,
- W. -Q. Wei,
- D. R. V. Edwards,
- T. L. Assimes,
- J. N. Hirschhorn,
- J. E. Below,
- C. R. Gignoux,
- A. E. Justice,
- R. J. F. Loos,
- Y. V. Sun,
- S. Raghavan,
- P. Deloukas,
- K. E. North,
- E. Marouli
Affiliations
- A. Papadopoulou
- William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London
- E. M. Litkowski
- VA Eastern Colorado Health Care System
- M. Graff
- Department of Epidemiology, University of North Carolina at Chapel Hill
- Z. Wang
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- R. A. J. Smit
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- G. Chittoor
- Department of Population Health Sciences, Geisinger
- I. Dinsmore
- Department of Genomic Health, Geisinger
- N. S. Josyula
- Department of Population Health Sciences, Geisinger
- M. Lin
- Colorado Center for Personalized Medicine, Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus
- J. Shortt
- Colorado Center for Personalized Medicine, Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus
- W. Zhu
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- S. L. Vedantam
- Program in Medical and Population Genetics, Broad Institute of Harvard and MIT
- L. Yengo
- Institute for Molecular Bioscience, The University of Queensland
- A. R. Wood
- Department of Biomedical Science, Centre of Membrane Interactions and Dynamics, University of Sheffield, Western Bank
- S. I. Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH
- I. A. Holm
- Division of Genetics and Genomics and Manton Center for Orphan Diseases Research, Boston Children’s Hospital, Department of Pediatrics, Harvard Medical School
- F. D. Mentch
- The Center for Applied Genomics, Children’s Hospital of Philadelphia
- H. Hakonarson
- The Center for Applied Genomics, Children’s Hospital of Philadelphia
- K. Kiryluk
- Department of Medicine, Division of Nephrology, Vagelos College of Physicians & Surgeons, Columbia University
- C. Weng
- Department of Biomedical Informatics, Vagelos College of Physicians & Surgeons, Columbia University
- G. P. Jarvik
- Department of Medicine (Medical Genetics) and Genome Sciences, University of Washington Medical Center
- D. Crosslin
- Division of Biomedical Informatics and Genomics, John W. Deming Department of Medicine, Tulane University, School of Medicine
- D. Carrell
- Kaiser Permanente Washington Health Research Institute
- I. J. Kullo
- Department of Cardiovascular Medicine and the Gonda Vascular Center, Mayo Clinic
- O. Dikilitas
- Department of Cardiovascular Medicine and the Gonda Vascular Center, Mayo Clinic
- M. G. Hayes
- Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University
- W. -Q. Wei
- Department of Biomedical Informatics, Vanderbilt University Medical Center
- D. R. V. Edwards
- Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center
- T. L. Assimes
- VA Palo Alto Health Care System
- J. N. Hirschhorn
- Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital
- J. E. Below
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- C. R. Gignoux
- Colorado Center for Personalized Medicine, Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus
- A. E. Justice
- Department of Population Health Sciences, Geisinger
- R. J. F. Loos
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Y. V. Sun
- Atlanta VA Health Care System
- S. Raghavan
- VA Eastern Colorado Health Care System
- P. Deloukas
- William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London
- K. E. North
- Department of Epidemiology, University of North Carolina at Chapel Hill
- E. Marouli
- William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London
- DOI
- https://doi.org/10.1038/s41525-025-00464-w
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 10
Abstract
Abstract We performed ancestry and sex specific Phenome Wide Association Studies (PheWAS) to explore disease related outcomes associated with genetically predicted height. This is the largest PheWAS on genetically predicted height involving up to 840,000 individuals of diverse ancestry. We explored European, African, East Asian ancestries and Hispanic population groups. Increased genetically predicted height is associated with hyperpotassemia and autism in the male cross-ancestry analysis. We report male-only European ancestry associations with anxiety disorders, post-traumatic stress and substance addiction and disorders. We identify a signal with benign neoplasm of other parts of digestive system in females. We report associations with a series of disorders, several with no prior evidence of association with height, involving mental disorders and the endocrine system. Our study suggests that increased genetically predicted height is associated with higher prevalence of many clinically relevant traits which has important implications for epidemiological and clinical disease surveillance and risk stratification.
