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.

Figure 1

Adjusted association between log-transformed TL and GPS in healthy African American children and adolescents in SAGE: San Francisco Bay Area, 2006–2015. Regression association adjusted for sex, age, genetic ancestry, maternal educational attainment, health insurance type and batch effects.

Figure 2

Results of GWAS for TL in healthy African American children and adolescents in SAGE: San Francisco Bay Area, 2006–2015. (A) Manhattan plot of the GWAS of TL with three SNPs relevant to telomere biology highlighted. Genome-wide significance threshold is indicated as red line (P = 1.2 × 10⁻⁷) and suggestive significance threshold is indicated as blue line (P = 2.3 × 10⁻⁶). (B) Expansion of 1 Mb flanking region around the top hit (rs1483898) with surrounding SNPs colored by amount of linkage disequilibrium with the top SNP, indicated by pairwise r² values from hg19/November 2014 1000 Genomes AFR.

Figure 3

Comparison of mean TL between rs1483898 genotypes in healthy African American children and adolescents in SAGE: San Francisco Bay Area, 2006–2015.