Dataset Information

Genetic Determinants of Telomere Length in African American Youth.

ABSTRACT: Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between 8 and 20 years old) and performed the first genome-wide association study of TL in this population. We were unable to replicate neither the 34 reported genetic associations found in adults nor the six genetic associations found in European children. However, we discovered a novel genome-wide significant association between TL and rs1483898 on chromosome 14. Our results underscore the importance of examining genetic associations with TL in diverse pediatric populations such as African Americans.

SUBMITTER: Zeiger AM

PROVIDER: S-EPMC6125592 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Genetic Determinants of Telomere Length in African American Youth.

Zeiger Andrew M AM White Marquitta J MJ Eng Celeste C Oh Sam S SS Witonsky Jonathan J Goddard Pagé C PC Contreras Maria G MG Elhawary Jennifer R JR Hu Donglei D Mak Angel C Y ACY Lee Eunice Y EY Keys Kevin L KL Samedy Lesly-Anne LA Risse-Adams Oona O Magaña Joaquín J Huntsman Scott S Salazar Sandra S Davis Adam A Meade Kelley K Brigino-Buenaventura Emerita E LeNoir Michael A MA Farber Harold J HJ Bibbins-Domingo Kirsten K Borrell Luisa N LN Burchard Esteban G EG

Scientific reports 20180905 1

Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants asso ...[more]

PMID: 30185882

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Project description:Summary Many epidemiologic studies have identified important relationships between leukocyte telomere length (LTL) with genetics and health. Most of these studies have been significantly limited in scope by focusing predominantly on individual diseases or restricted to GWAS analysis. Using two large patient populations derived from Vanderbilt University and Marshfield Clinic biobanks linked to genomic and phenomic data from medical records, we investigated the inter-relationship between LTL, genomics, and human health. Our GWAS confirmed 11 genetic loci previously associated with LTL and two novel loci in SCNN1D and PITPNM1. PheWAS of LTL identified 67 distinct clinical phenotypes associated with both short and long LTL. We demonstrated that several diseases associated with LTL were related to one another but were largely independent from LTL genetics. Age of death was correlated with LTL independent of age. Those with very short LTL (<−1.5 standard deviation [SD]) died 10.4 years (p < 0.0001) younger than those with average LTL (±0.5 SD; mean age of death = 74.2 years). Likewise, those with very long LTL (>1.5 SD) died 1.9 years (p = 0.0175) younger than those with average LTL. This is consistent with the PheWAS results showing diseases associating with both short and long LTL. Finally, we estimated that the genome (12.8%) and age (8.5%) explain the largest proportion of LTL variance, whereas the phenome (1.5%) and sex (0.9%) explained a smaller fraction. In total, 23.7% of LTL variance was explained. These observations provide the rationale for expanded research to understand the multifaceted correlations between TL biology and human health over time, leading to effective LTL usage in medical applications. Most studies studying telomere length are limited in scope by focusing on an individual disease or genomic analysis. Using two large patient populations derived from Vanderbilt University and Marshfield Clinic biobanks we provide one of the first comprehensive studies that examine the inter-relationship between telomere length, genomics, and human health.

Dataset Information

Genetic Determinants of Telomere Length in African American Youth.

Publications

Genetic Determinants of Telomere Length in African American Youth.

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