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

TitleRelationship of genetic determinants of height with cardiometabolic and pulmonary traits in the Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2018
AuthorsSofer T, Moon J-Y, Isasi CR, Qi Q, Shah NA, Kaplan RC, Kuniholm MH
JournalInt J Epidemiol
Volume47
Issue6
Pagination2059-2069
Date Published2018 12 01
ISSN1464-3685
KeywordsAdult, ankle brachial index, Body Height, Cardiovascular System, Cholesterol, Correlation of Data, Cross-Cultural Comparison, Female, Forced Expiratory Flow Rates, genome-wide association study, Glomerular Filtration Rate, Glucose Tolerance Test, Hispanic Americans, Humans, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Public Health, Pulmonary Elimination, Research Design, United States
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.

DOI10.1093/ije/dyy177
Alternate JournalInt J Epidemiol
PubMed ID30137430
PubMed Central IDPMC6280956
Grant ListN01HC65236 / HL / NHLBI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
UL1 TR002556 / TR / NCATS NIH HHS / United States
MS#: 
0611
Manuscript Lead/Corresponding Author Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
ECI: 
Manuscript Status: 
Published