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Original Article
Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal
  1. Dayana A Delgado1,
  2. Chenan Zhang1,2,
  3. Lin S Chen1,
  4. Jianjun Gao3,
  5. Shantanu Roy1,4,
  6. Justin Shinkle1,
  7. Mekala Sabarinathan1,
  8. Maria Argos5,
  9. Lin Tong1,
  10. Alauddin Ahmed6,
  11. Tariqul Islam6,
  12. Muhammad Rakibuz-Zaman6,
  13. Golam Sarwar6,
  14. Hasan Shahriar6,
  15. Mahfuzar Rahman7,
  16. Mohammad Yunus8,
  17. Farzana Jasmine1,
  18. Muhammad G Kibriya1,
  19. Habibul Ahsan1,9,10,11,
  20. Brandon L Pierce1,9,10
  1. 1 Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA
  2. 2 Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
  3. 3 Department of Psychiatry, University of California San Diego, La Jolla, California, USA
  4. 4 Division of Foodborne, Waterborne, and Environmental Diseases, Center for Disease Control, Atlanta, Georgia, USA
  5. 5 Division of Epidemiology and Biostatistics, University of Illinois, Chicago, Illinois, USA
  6. 6 UChicago Research Bangladesh, Dhaka, Bangladesh
  7. 7 Research and Evaluation Division, BRAC, Dhaka, Bangladesh
  8. 8 Health Systems and Population Studies Division, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
  9. 9 Department of Human Genetics, University of Chicago, Chicago, Illinois, USA
  10. 10 Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA
  11. 11 Department of Medicine, University of Chicago, Chicago, Illinois, USA
  1. Correspondence to Dr Brandon L Pierce, Department of Public Health Sciences, The University of Chicago, 5841 South Maryland Avenue, MC2000 Chicago, IL 60637, USA; brandonpierce{at}uchicago.edu

Abstract

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.

  • aging
  • telomere length
  • heritability
  • ancestry
  • genetic variant

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors Design of telomere length studies within Heals and Best: BLP; design of Heals and Best studies: HA; generation of genetic and molecular data: MGK, SR, MR, JS and MS; collection of data from study participants: MA, MR-Z, AA, TI, GS, MR and MY; quality control for telomere length measures: CZ; SNP data quality control and imputation: CZ and LT; data analysis and interpretation: BLP and DD; drafting the article: DD; critical revision of the article: all authors.

  • Funding This work was supported by the National Institutes of Health (R01ES020506, U01 HG007601, P42 ES10349, R01 CA107431, R01 CA102484, P30CA014599).

  • Competing interests None declared.

  • Ethics approval The institutional review boards of the University of Chicago and Columbia University, and the ethical committee of the Bangladesh Medical Research Council reviewed and approved these projects.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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