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- Title
Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies.
- Authors
Dorajoo, Rajkumar; Chang, Xuling; Gurung, Resham Lal; Li, Zheng; Wang, Ling; Wang, Renwei; Beckman, Kenneth B.; Adams-Haduch, Jennifer; M, Yiamunaa; Liu, Sylvia; Meah, Wee Yang; Sim, Kar Seng; Lim, Su Chi; Friedlander, Yechiel; Liu, Jianjun; van Dam, Rob M.; Yuan, Jian-Min; Koh, Woon-Puay; Khor, Chiea Chuen; Heng, Chew-Kiat
- 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. Shortening of leukocyte telomere length (LTL) is associated with age and increased risk for various chronic diseases. Here, the authors report genome-wide association studies for LTL in Singaporean Chinese populations and find that longer LTL associates with less severe outcomes of respiratory disease phenotypes.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-10443-2