|Relationship of genetic determinants of height with cardiometabolic and pulmonary traits in the Hispanic Community Health Study/Study of Latinos.
|Sofer T, Moon J-Y, Isasi CR, Qi Q, Shah NA, Kaplan RC, Kuniholm MH
|Int J Epidemiol
|2018 Dec 01
|Adult, 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 or Latino, Humans, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Public Health, Pulmonary Elimination, Research Design, United States
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.
|Int J Epidemiol
|PubMed Central ID
|N01HC65236 / 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
Relationship of genetic determinants of height with cardiometabolic and pulmonary traits in the Hispanic Community Health Study/Study of Latinos.