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Relationship of genetic determinants of height with cardiometabolic and pulmonary traits in the Hispanic Community Health Study/Study of Latinos

Year: 2018
Type: article
Abstract: Background: Associations of adult height with cardiometabolic and pulmonary traits have been studied in majority European ancestry populations using Mendelian randomization and polygenic risk score (PRS) analysis. The standard PRS approach entails creating a PRS for height using variants identified in prior genome-wide association studies (GWAS). It is unclear how well the standard PRS approach performs in non-European populations and whether height-trait associations observed in Europeans are also observed in other populations. Methods: In the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we used: (i) the standard approach to create a PRS for height (PRS1) and (ii) a novel approach to optimize the selection of variants from previously established height association loci to better explain height in HCHS/SOL (PRS2). We also estimated the extent to which PRS-trait associations were independent or mediated by the PRS effect on height. Results: In 7539 women and 5245 men, PRS1 and PRS2 explained 9 and 29% of the variance in measured height, respectively. Both PRS1 and PRS2 were associated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/ FVC ratio, total cholesterol and 2-hour oral glucose-tolerance test insulin levels. Additionally, PRS2 was associated with estimated glomerular filtration rate and ankle brachial index. Both PRS1 and PRS2 had pleiotropic associations with FEV1/ FVC ratio in mediation analyses. Conclusions: Associations of polygenic scores of height with measures of lung function and cholesterol were consistent with those observed in prior studies of majority European ancestry populations. Mediation analysis may augment standard PRS approaches to disentangle pleiotropic and mediated effects.
DOI: 10.1093/ije/dyy177
Authors: Tamar Sofer, Jee-Young Moon, Carmen R Isasi, Qibin Qi, Neomi A Shah, Robert C Kaplan, Mark H Kuniholm
Institutions: Brigham and Women's Hospital, Harvard University, Albert Einstein College of Medicine, Icahn School of Medicine at Mount Sinai, Fred Hutch Cancer Center, University at Albany, State University of New York
Language: English
Subfield: Genetics
Open Access status: bronze
Funders: Office of Dietary Supplements, University of Miami, University of North Carolina, Northwestern University, San Diego State University, University of Washington, National Institutes of Health, Albert Einstein College of Medicine, Yeshiva University, Gillings School of Public Health, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Center on Minority Health and Health Disparities, National Center for Advancing Translational Sciences
Awards: G1064233440, G1081972346, G1312369436, Hispanic Community Health Study, G1455175283, G1888983140, G2128161193, G2135211244, G2215135821, G2466919156, HISPANIC COMMUNITY HEALTH STUDY - FIELD CENTER, G2644289446, Hispanic Community Health Study, Hispanic Community Health Study, G5129651400, HISPANIC COMMUNITY HEALTH STUDY - COORDINATING CENTER, G543802643, Clinical and Translational Science Award, G820454163
OpenAlex ID: W2888672888
FWCI: 1.073
Cites: 32
Cited by: 15
Related to: 10