1. Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies.
- Author
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Dorajoo R, Chang X, Gurung RL, Li Z, Wang L, Wang R, Beckman KB, Adams-Haduch J, M Y, Liu S, Meah WY, Sim KS, Lim SC, Friedlander Y, Liu J, van Dam RM, Yuan JM, Koh WP, Khor CC, and Heng CK
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Prospective Studies, Respiratory Tract Infections genetics, Singapore, White People genetics, Young Adult, Asian People genetics, DNA Repair genetics, Leukocytes metabolism, Telomere metabolism, Telomere Homeostasis genetics
- 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.- Published
- 2019
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