Journal Article

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

Chang, Xuling, Li, Zheng, Liu, Jianjun, Yuan, Jian-Min, Koh, Woon-Puay, Dorajoo, Rajkumar, Gurung, Resham Lal, Wang, Ling, Lim, Su Chi, Liu, Sylvia, Beckman, Kenneth B., Meah, Wee Yang, van Dam, Rob M., Sim, Kar Seng, Friedlander, Yechiel, M, Yiamunaa, Khor, Chiea Chuen, Heng, Chew-Kiat, Wang, Renwei, Adams-Haduch, Jennifer

2019

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/43 / 45/77 / 631/208 / 631/208/205/2138 / 631/337/103/560 / 692/308/2056 / Adult / Aged / Aged, 80 and over / Asian People - genetics / Cohort Studies / Deoxyribonucleic acid / DNA / DNA repair / DNA Repair - genetics / Ethnic factors / Female / Genetic factors / Genome-wide association studies / Genome-Wide Association Study / Genomes / Homeostasis / Humanities and Social Sciences / Humans / Leukocytes / Leukocytes - metabolism / Loci / Male / Middle Aged / multidisciplinary / Nkx2.3 protein / Poly(ADP-ribose) polymerase / Population genetics / Population studies / Prospective Studies / Respiratory diseases / Respiratory Tract Infections - genetics / Science / Science (multidisciplinary) / Singapore / Single-nucleotide polymorphism / Telomere - metabolism / Telomere Homeostasis - genetics / White People - genetics / Young Adult