TY - JOUR
T1 - Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies
AU - Dorajoo, Rajkumar
AU - Chang, Xuling
AU - Gurung, Resham Lal
AU - Li, Zheng
AU - Wang, Ling
AU - Wang, Renwei
AU - Beckman, Kenneth B.
AU - Adams-Haduch, Jennifer
AU - M, Yiamunaa
AU - Liu, Sylvia
AU - Meah, Wee Yang
AU - Sim, Kar Seng
AU - Lim, Su Chi
AU - Friedlander, Yechiel
AU - Liu, Jianjun
AU - van Dam, Rob M.
AU - Yuan, Jian Min
AU - Koh, Woon Puay
AU - Khor, Chiea Chuen
AU - Heng, Chew Kiat
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85066940943&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-10443-2
DO - 10.1038/s41467-019-10443-2
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 31171785
AN - SCOPUS:85066940943
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2491
ER -
