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

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

doi:10.1038/s41467-019-10443-2

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

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

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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.

Original language	English (US)
Article number	2491
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10443-2
State	Published - Dec 1 2019

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© 2019, The Author(s).

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Dorajoo, R., Chang, X., Gurung, R. L., Li, Z., Wang, L., Wang, R., Beckman, K. B., Adams-Haduch, J., M, Y., Liu, S., Meah, W. Y., Sim, K. S., Lim, S. C., Friedlander, Y., Liu, J., van Dam, R. M., Yuan, J. M., Koh, W. P., Khor, C. C., & Heng, C. K. (2019). Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies. Nature communications, 10(1), Article 2491. https://doi.org/10.1038/s41467-019-10443-2

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 & Heng, CK 2019, 'Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies', Nature communications, vol. 10, no. 1, 2491. https://doi.org/10.1038/s41467-019-10443-2

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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.",

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

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AU - van Dam, Rob M.

AU - Yuan, Jian Min

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AU - Khor, Chiea Chuen

AU - Heng, Chew Kiat

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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.

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

Abstract

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