Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height
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.
Authors
- Joel N. Hirschhorn (ORCID: https://orcid.org/0000-0002-1650-7901)
- Ingrid A. Holm (ORCID: https://orcid.org/0000-0003-4712-8821)
- Themistocles L. Assimes (ORCID: https://orcid.org/0000-0003-2349-0009)
- Chunhua Weng (ORCID: https://orcid.org/0000-0002-9624-0214)
- Sridharan Raghavan (ORCID: https://orcid.org/0000-0003-0643-4873)
- Ruth J. F. Loos (ORCID: https://orcid.org/0000-0002-8532-5087)
- David R. Crosslin (ORCID: https://orcid.org/0000-0003-3658-9059)
- Wei-Qi Wei (ORCID: https://orcid.org/0000-0003-4985-056X)
- Meng Lin (ORCID: https://orcid.org/0000-0003-4603-0718)
- Loïc Yengo (ORCID: https://orcid.org/0000-0002-4272-9305)
- Andrew R. Wood (ORCID: https://orcid.org/0000-0003-1726-948X)
- Jennifer Elizabeth Below (ORCID: https://orcid.org/0000-0002-1346-1872)
- Geetha Chittoor (ORCID: https://orcid.org/0000-0001-6443-6012)
- Frank Mentch (ORCID: https://orcid.org/0000-0003-4889-6961)
- Areti Papadopoulou (ORCID: https://orcid.org/0000-0003-3158-7951)
- Yan V. Sun (ORCID: https://orcid.org/0000-0002-2838-1824)
- David Carrell (ORCID: https://orcid.org/0000-0002-8471-0928)
- Digna R. Velez Edwards (ORCID: https://orcid.org/0000-0001-5293-0056)
- Elizabeth Litkowski (ORCID: https://orcid.org/0000-0002-7079-696X)
- Mariaelisa Graff (ORCID: https://orcid.org/0000-0001-6380-1735)
- Krzysztof Kiryluk (ORCID: https://orcid.org/0000-0002-5047-6715)
- Sailaja Vedantam (ORCID: https://orcid.org/0000-0003-3892-7461)
- Navya Shilpa Josyula (ORCID: https://orcid.org/0000-0003-2782-8812)
- G.P. Jarvik
- Roelof A. J. Smit (ORCID: https://orcid.org/0000-0001-9822-6726)
- M. Geoffrey Hayes (ORCID: https://orcid.org/0000-0002-4617-3981)
- C. R. Gignoux
- Anne E. Justice (ORCID: https://orcid.org/0000-0002-8903-8712)
- Kari E. North (ORCID: https://orcid.org/0000-0002-8903-0366)
- John Shortt
- Iftikhar J. Kullo (ORCID: https://orcid.org/0000-0002-6524-3471)
- Sonja I. Berndt (ORCID: https://orcid.org/0000-0001-5230-0652)
- Ian Dinsmore (ORCID: https://orcid.org/0000-0002-6134-8997)
- Panos Deloukas (ORCID: https://orcid.org/0000-0001-9251-070X)
- Ozan Dikilitas (ORCID: https://orcid.org/0000-0002-9906-8608)
- Håkon Håkonarson (ORCID: https://orcid.org/0000-0003-2814-7461)
- Eirini Marouli (ORCID: https://orcid.org/0000-0001-6179-1609)
- Zhe Wang (ORCID: https://orcid.org/0000-0002-8046-4969)
- Wanying Zhu (ORCID: https://orcid.org/0000-0002-2673-3048)
Institutions
- Broad Institute (US)
- Northwestern University (US)
- University of North Carolina at Chapel Hill (US)
- Tulane University (US)
- University of Copenhagen (DK)
- Boston Children's Hospital (US)
- Mayo Clinic (US)
- Children's Hospital of Philadelphia (US)
- Harvard University (US)
- Kaiser Permanente Washington Health Research Institute (US)
- Emory University (US)
- The University of Queensland (AU)
- Queen Mary University of London (GB)
- VA Palo Alto Health Care System (US)
- Leiden University Medical Center (NL)
- Novo Nordisk Foundation (DK)
- University of Washington Medical Center (US)
- Child Health and Development Institute (US)
- National Cancer Institute (US)
- Pediatrics and Genetics (US)
- VA Eastern Colorado Health Care System (US)
- Atlanta VA Health Care System (US)
- William Harvey Research Institute (GB)
- Genomic Health (United States) (US)
- Division of Cancer Epidemiology and Genetics
- University of Colorado Anschutz Medical Campus (US)
- Geisinger Health System (US)
- Columbia University (US)
- Vanderbilt University Medical Center (US)
- University of Sheffield (GB)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- npj Genomic Medicine
- Published
- 2025-02-27
- DOI
- https://doi.org/10.1038/s41525-025-00464-w
- Citations
- 1
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- U.S. Department of Veterans Affairs
- Brigham and Women's Hospital
- Boettcher Foundation
- Office of Research and Development
- Children's Hospital of Philadelphia
- Vanderbilt University
- Northwestern University
- Cincinnati Children's Hospital Medical Center
- University of Washington
- Vanderbilt University Medical Center
- Broad Institute
- Georgia Clinical and Translational Science Alliance
- National Institute for Health and Care Research
- British Heart Foundation
- Novo Nordisk
- Novo Nordisk Fonden
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute
- National Institute of Diabetes and Digestive and Kidney Diseases