Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height

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...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:npj Genomic Medicine
Online Access:https://doi.org/10.1038/s41525-025-00464-w
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author 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
author_facet 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
author_sort A. Papadopoulou
collection DOAJ
description 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.
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spelling doaj-art-05001f87f5e34497bced3d3551cdfd012025-08-20T02:01:38ZengNature Portfolionpj Genomic Medicine2056-79442025-02-0110111010.1038/s41525-025-00464-wInsights from the largest diverse ancestry sex-specific disease map for genetically predicted heightA. Papadopoulou0E. M. Litkowski1M. Graff2Z. Wang3R. A. J. Smit4G. Chittoor5I. Dinsmore6N. S. Josyula7M. Lin8J. Shortt9W. Zhu10S. L. Vedantam11L. Yengo12A. R. Wood13S. I. Berndt14I. A. Holm15F. D. Mentch16H. Hakonarson17K. Kiryluk18C. Weng19G. P. Jarvik20D. Crosslin21D. Carrell22I. J. Kullo23O. Dikilitas24M. G. Hayes25W. -Q. Wei26D. R. V. Edwards27T. L. Assimes28J. N. Hirschhorn29J. E. Below30C. R. Gignoux31A. E. Justice32R. J. F. Loos33Y. V. Sun34S. Raghavan35P. Deloukas36K. E. North37E. Marouli38William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of LondonVA Eastern Colorado Health Care SystemDepartment of Epidemiology, University of North Carolina at Chapel HillThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiDepartment of Population Health Sciences, GeisingerDepartment of Genomic Health, GeisingerDepartment of Population Health Sciences, GeisingerColorado Center for Personalized Medicine, Department of Biomedical Informatics, University of Colorado Anschutz Medical CampusColorado Center for Personalized Medicine, Department of Biomedical Informatics, University of Colorado Anschutz Medical CampusVanderbilt Genetics Institute, Vanderbilt University Medical CenterProgram in Medical and Population Genetics, Broad Institute of Harvard and MITInstitute for Molecular Bioscience, The University of QueenslandDepartment of Biomedical Science, Centre of Membrane Interactions and Dynamics, University of Sheffield, Western BankDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIHDivision of Genetics and Genomics and Manton Center for Orphan Diseases Research, Boston Children’s Hospital, Department of Pediatrics, Harvard Medical SchoolThe Center for Applied Genomics, Children’s Hospital of PhiladelphiaThe Center for Applied Genomics, Children’s Hospital of PhiladelphiaDepartment of Medicine, Division of Nephrology, Vagelos College of Physicians & Surgeons, Columbia UniversityDepartment of Biomedical Informatics, Vagelos College of Physicians & Surgeons, Columbia UniversityDepartment of Medicine (Medical Genetics) and Genome Sciences, University of Washington Medical CenterDivision of Biomedical Informatics and Genomics, John W. Deming Department of Medicine, Tulane University, School of MedicineKaiser Permanente Washington Health Research InstituteDepartment of Cardiovascular Medicine and the Gonda Vascular Center, Mayo ClinicDepartment of Cardiovascular Medicine and the Gonda Vascular Center, Mayo ClinicDivision of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern UniversityDepartment of Biomedical Informatics, Vanderbilt University Medical CenterDivision of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University Medical CenterVA Palo Alto Health Care SystemDivision of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s HospitalVanderbilt Genetics Institute, Vanderbilt University Medical CenterColorado Center for Personalized Medicine, Department of Biomedical Informatics, University of Colorado Anschutz Medical CampusDepartment of Population Health Sciences, GeisingerThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiAtlanta VA Health Care SystemVA Eastern Colorado Health Care SystemWilliam Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of LondonDepartment of Epidemiology, University of North Carolina at Chapel HillWilliam Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of LondonAbstract 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.https://doi.org/10.1038/s41525-025-00464-w
spellingShingle 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
Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height
npj Genomic Medicine
title Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height
title_full Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height
title_fullStr Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height
title_full_unstemmed Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height
title_short Insights from the largest diverse ancestry sex-specific disease map for genetically predicted height
title_sort insights from the largest diverse ancestry sex specific disease map for genetically predicted height
url https://doi.org/10.1038/s41525-025-00464-w
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