Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies

Nat Commun. 2019 Jun 6;10(1):2491. doi: 10.1038/s41467-019-10443-2.

Abstract

Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci (P < 5 × 10-8). Several of these contain candidate genes (TINF2, PARP1, TERF1, ATM and POT1) with potential roles in telomere biology and DNA repair mechanisms. Meta-analyses with additional 37,505 European individuals reveals six more genome-wide loci, including associations at MPHOSPH6, NKX2-3 and TYMS. We demonstrate that longer LTL associates with protection against respiratory disease mortality [HR = 0.854(0.804-0.906), P = 1.88 × 10-7] in the Singaporean Chinese samples. We further show that the LTL reducing SNP rs7253490 associates with respiratory infections (P = 7.44 × 10-4) although this effect may not be strongly mediated through LTL. Our data expands on the genetic basis of LTL and may indicate on a potential role of LTL in immune competence.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics*
  • Cohort Studies
  • DNA Repair / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Leukocytes / metabolism*
  • Male
  • Middle Aged
  • Prospective Studies
  • Respiratory Tract Infections / genetics
  • Singapore
  • Telomere / metabolism*
  • Telomere Homeostasis / genetics*
  • White People / genetics
  • Young Adult