Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jan;55(1):64-71.
doi: 10.1136/jmedgenet-2017-104922. Epub 2017 Nov 18.

Genome-wide Association Study of Telomere Length Among South Asians Identifies a Second RTEL1 Association Signal

Free PMC article

Genome-wide Association Study of Telomere Length Among South Asians Identifies a Second RTEL1 Association Signal

Dayana A Delgado et al. J Med Genet. .
Free PMC article


Background: Leucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry.

Objective: This study aims to enhance our understanding of genetic determinants of TL across populations.

Methods: We performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes.

Results: Our results replicate previously reported associations in the TERC and TERT regions (P=2.2×10-8 and P=6.4×10-6, respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10-7) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (≥0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 (ZNF208) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only.

Conclusions: In this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus.

Keywords: aging; ancestry; genetic variant; heritability; telomere length.

Conflict of interest statement

Competing interests: None declared.


Figure 1
Figure 1
Summary plots of GWAS results. (A) Quantile–quantile (Q–Q) plot of the negative logarithm of the observed (y-axis) and expected (x-axis) P value for each SNP, where the red line represents the null hypothesis of no associations. B) Manhattan plot showing association signals in TERC, TERT and RTEL1 regions. The –log10(P values) are plotted against physical position for 6.3 million SNPs. The red line indicates the genome-wide significance threshold at P=5×10–8. We used a threshold of P=1×10–5 to define suggestive signals (blue line). GWAS, genome-wide association study.
Figure 2
Figure 2
Regional association plots for loci associated with TL. (A–cC) The –log10(P Value) for each SNP is plotted against the base-pair position along each chromosome (Mb). For each locus, the lead SNP is represented in purple; SNPs are colour coded by level of linkage disequilibrium (r2) to the lead SNP, and the blue lines represent recombination rates (cM/Mb). TL, telomere length.

Similar articles

See all similar articles

Cited by 8 articles

  • Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.
    Li C, Stoma S, Lotta LA, Warner S, Albrecht E, Allione A, Arp PP, Broer L, Buxton JL, Da Silva Couto Alves A, Deelen J, Fedko IO, Gordon SD, Jiang T, Karlsson R, Kerrison N, Loe TK, Mangino M, Milaneschi Y, Miraglio B, Pervjakova N, Russo A, Surakka I, van der Spek A, Verhoeven JE, Amin N, Beekman M, Blakemore AI, Canzian F, Hamby SE, Hottenga JJ, Jones PD, Jousilahti P, Mägi R, Medland SE, Montgomery GW, Nyholt DR, Perola M, Pietiläinen KH, Salomaa V, Sillanpää E, Suchiman HE, van Heemst D, Willemsen G, Agudo A, Boeing H, Boomsma DI, Chirlaque MD, Fagherazzi G, Ferrari P, Franks P, Gieger C, Eriksson JG, Gunter M, Hägg S, Hovatta I, Imaz L, Kaprio J, Kaaks R, Key T, Krogh V, Martin NG, Melander O, Metspalu A, Moreno C, Onland-Moret NC, Nilsson P, Ong KK, Overvad K, Palli D, Panico S, Pedersen NL, Penninx BWJH, Quirós JR, Jarvelin MR, Rodríguez-Barranco M, Scott RA, Severi G, Slagboom PE, Spector TD, Tjonneland A, Trichopoulou A, Tumino R, Uitterlinden AG, van der Schouw YT, van Duijn CM, Weiderpass E, Denchi EL, Matullo G, Butterworth AS, Danesh J, Samani NJ, Wareham NJ, Nelson CP, Langenberg C, Codd V. Li C, et al. Am J Hum Genet. 2020 Mar 5;106(3):389-404. doi: 10.1016/j.ajhg.2020.02.006. Epub 2020 Feb 27. Am J Hum Genet. 2020. PMID: 32109421
  • Genetic variants in RTEL1 influencing telomere length are associated with prostate cancer risk.
    Gu CY, Jin SM, Qin XJ, Zhu Y, Bo D, Lin GW, Shi GH, Ye DW. Gu CY, et al. J Cancer. 2019 Oct 15;10(24):6170-6174. doi: 10.7150/jca.35917. eCollection 2019. J Cancer. 2019. PMID: 31762827 Free PMC article.
  • The Genetic Architecture of Bovine Telomere Length in Early Life and Association With Animal Fitness.
    Ilska-Warner JJ, Psifidi A, Seeker LA, Wilbourn RV, Underwood SL, Fairlie J, Whitelaw B, Nussey DH, Coffey MP, Banos G. Ilska-Warner JJ, et al. Front Genet. 2019 Oct 25;10:1048. doi: 10.3389/fgene.2019.01048. eCollection 2019. Front Genet. 2019. PMID: 31749836 Free PMC article.
  • Common genetic variation and risk of osteosarcoma in a multi-ethnic pediatric and adolescent population.
    Zhang C, Hansen HM, Semmes EC, Gonzalez-Maya J, Morimoto L, Wei Q, Eward WC, DeWitt SB, Hurst JH, Metayer C, de Smith AJ, Wiemels JL, Walsh KM. Zhang C, et al. Bone. 2020 Jan;130:115070. doi: 10.1016/j.bone.2019.115070. Epub 2019 Sep 13. Bone. 2020. PMID: 31525475
  • Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies.
    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. Dorajoo R, et al. Nat Commun. 2019 Jun 6;10(1):2491. doi: 10.1038/s41467-019-10443-2. Nat Commun. 2019. PMID: 31171785 Free PMC article.
See all "Cited by" articles


    1. Blackburn EH, Epel ES, Lin J. Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science 2015;350:1193–8. 10.1126/science.aab3389 - DOI - PubMed
    1. Shawi M, Autexier C. Telomerase, senescence and ageing. Mech Ageing Dev 2008;129:3–10. 10.1016/j.mad.2007.11.007 - DOI - PubMed
    1. Cong YS, Wright WE, Shay JW. Human telomerase and its regulation. Microbiol Mol Biol Rev 2002;66:407–25. 10.1128/MMBR.66.3.407-425.2002 - DOI - PMC - PubMed
    1. Huang Y, Liang P, Liu D, Huang J, Songyang Z. Telomere regulation in pluripotent stem cells. Protein Cell 2014;5:194–202. 10.1007/s13238-014-0028-1 - DOI - PMC - PubMed
    1. Kalmbach K, Robinson LG, Wang F, Liu L, Keefe D. Telomere length reprogramming in embryos and stem cells. Biomed Res Int 2014;2014:1–7. 10.1155/2014/925121 - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources