Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
Year: 2019
Type: review
Study design: Observational Study
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.
Source: Nature Communications
Authors: Rajkumar Dorajoo, Xuling Chang, Resham Lal Gurung, Zheng Li, Ling Wang, Renwei Wang, Kenneth B. Beckman, Jennifer Adams-Haduch, Yiamunaa M, Sylvia Liu, Wee Yang Meah, Kar Seng Sim, Su Chi Lim, Yechiel Friedlander, Jianjun Liu, Rob M. van Dam, Jian-Min Yuan, Woon-Puay Koh, Chiea Chuen Khor, Chew-Kiat Heng
Institutions: Agency for Science, Technology and Research, Genome Institute of Singapore, National University of Singapore, National University Health System, Khoo Teck Puat Hospital, University of Pittsburgh, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, University of Minnesota, Hebrew University of Jerusalem, SingHealth Duke-NUS Academic Medical Centre, Duke-NUS Medical School, Singapore National Eye Center, Singapore Eye Research Institute
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: Prospective studies of cancer etiology and prevention in Shanghai and Singapore, THE SINGAPORE COHORT STUDY OF DIET AND CANCER, G2821390757, G3727305500, G3954528190, G51409772, G6911639505, G7091346327, Cancer epidemiology cohorts in Shanghai and Singapore , G7508486575, G8965643212, G9000120430
OpenAlex ID: W2948278421