A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program.

Autor: Raghavan S; Medicine Service, Veterans Affairs Eastern Colorado Health Care System, Aurora, Colorado, United States of America.; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America., Huang J; School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, Guangdong, China., Tcheandjieu C; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America., Huffman JE; Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America., Litkowski E; Medicine Service, Veterans Affairs Eastern Colorado Health Care System, Aurora, Colorado, United States of America., Liu C; Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America.; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America., Ho YA; Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America., Hunter-Zinck H; Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America., Zhao H; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, United States of America.; Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut, United States of America., Marouli E; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom., North KE; Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America., Lange E; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America., Lange LA; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America., Voight BF; Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.; Institute of Translational Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America., Gaziano JM; Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America., Pyarajan S; Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America., Hauser ER; Cooperative Studies Program Epidemiology Center- Durham, Durham Veterans Affairs Health Care System, Durham, North Carolina, United States of America.; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, United States of America., Tsao PS; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America., Wilson PWF; Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America.; Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, United States of America., Chang KM; Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America., Cho K; Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America., O'Donnell CJ; Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America., Sun YV; Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America.; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America., Assimes TL; Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2022 Jun 02; Vol. 18 (6), pp. e1010193. Date of Electronic Publication: 2022 Jun 02 (Print Publication: 2022).
DOI: 10.1371/journal.pgen.1010193
Abstrakt: Background: Height has been associated with many clinical traits but whether such associations are causal versus secondary to confounding remains unclear in many cases. To systematically examine this question, we performed a Mendelian Randomization-Phenome-wide association study (MR-PheWAS) using clinical and genetic data from a national healthcare system biobank.
Methods and Findings: Analyses were performed using data from the US Veterans Affairs (VA) Million Veteran Program in non-Hispanic White (EA, n = 222,300) and non-Hispanic Black (AA, n = 58,151) adults in the US. We estimated height genetic risk based on 3290 height-associated variants from a recent European-ancestry genome-wide meta-analysis. We compared associations of measured and genetically-predicted height with phenome-wide traits derived from the VA electronic health record, adjusting for age, sex, and genetic principal components. We found 345 clinical traits associated with measured height in EA and an additional 17 in AA. Of these, 127 were associated with genetically-predicted height at phenome-wide significance in EA and 2 in AA. These associations were largely independent from body mass index. We confirmed several previously described MR associations between height and cardiovascular disease traits such as hypertension, hyperlipidemia, coronary heart disease (CHD), and atrial fibrillation, and further uncovered MR associations with venous circulatory disorders and peripheral neuropathy in the presence and absence of diabetes. As a number of traits associated with genetically-predicted height frequently co-occur with CHD, we evaluated effect modification by CHD status of genetically-predicted height associations with risk factors for and complications of CHD. We found modification of effects of MR associations by CHD status for atrial fibrillation/flutter but not for hypertension, hyperlipidemia, or venous circulatory disorders.
Conclusions: We conclude that height may be an unrecognized but biologically plausible risk factor for several common conditions in adults. However, more studies are needed to reliably exclude horizontal pleiotropy as a driving force behind at least some of the MR associations observed in this study.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CJO is a full-time employee of Novartis Institutes of Biomedical Research. The remaining authors have declared that no competing interests exist.
Databáze: MEDLINE
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