Genetic Determinants of Leucocyte Telomere Length in Children: a Neglected and Challenging Field

Abstract

(2015)

Genetic Determinants of Telomere Length in African American Youth

“…Our results are consistent with recent studies in pediatric populations 29,30 that did not replicate variants associated with TL in adults 17–26 , suggesting that these variants may not play a significant role in the regulation of TL during the first two decades of growth and development. However, we were also unable to replicate genetic variants associated with TL in a population of European children 30 , highlighting potential population-specific effects of genetic associations with TL. Lastly, we identified a genome-wide significant variant, rs1483898, and 41 suggestively associated variants within genes relevant to telomere biology in a GWAS for TL in African American children and adolescents.…”

“…None of the variants from either the adult or pediatric studies were significantly associated with TL in our study population (P > 0.05). To determine whether the combined effect of the six previously discovered pediatric variants was associated with TL in our study population, we calculated a weighted genetic prediction score (GPS) by aggregating the allele associated with longer TL in European children weighted by the published β-coefficient 30 . There was no significant association between the GPS and TL in our study population of African American children and adolescents (β = 0.377, P = 0.150, Fig.…”

“…Over 30 studies have used these variants as genetic proxies for TL through Mendelian randomization approaches to address reverse causation when examining association between TL and disease in diseased patients 17,27,28 . However, recent studies in Chinese newborns and European children have failed to replicate these variants, suggesting that they are not generalizable across age groups 29,30 . One study, by Stathopoulou et al ., reported six novel genetic variants associated with TL in European children (age 4–18 years) not previously discovered in adult telomere studies 30 .…”

“…However, recent studies in Chinese newborns and European children have failed to replicate these variants, suggesting that they are not generalizable across age groups 29,30 . One study, by Stathopoulou et al ., reported six novel genetic variants associated with TL in European children (age 4–18 years) not previously discovered in adult telomere studies 30 . Replication of these six genetic variants has not yet been attempted.…”

Telomere length change plateaus at 4 years of age in Latino children: associations with baseline length and maternal change

“…Additionally, studies suggest that the genetic variants associated with leucocyte telomere length in adults do not determine leukocyte telomere length in children. Different genetic determinants impact child compared with adult telomere length (Stathopoulou et al 2015). Stathopoulou et al suggest that single nucleotide polymorphisms (SNPs), associated with generally minor effects on telomere length in adulthood, may determine adult telomere maintenance processes versus different SNPs which are responsible for regulating telomere attrition in childhood.…”