Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to 
Leukocyte Telomere Length

Li, C.; Stoma, S.; Lotta, L. A.; Warner, S.; Albrecht, E.; Allione, A.; Arp, P. P.; Broer, L.; Buxton, J. L.; Da Silva Couto Alves, A.; Deelen, J.; Fedko, I. O.; Gordon, S. D.; Jiang, T.; Karlsson, R.; Kerrison, N.; Loe, T. K.; Mangino, M.; Milaneschi, Y.; Miraglio, B.; Pervjakova, N.; Russo, A.; Surakka, I.; van der Spek, A.; Verhoeven, J. E.; Amin, N.; Beekman, M.; Blakemore, A. I.; Canzian, F.; Hamby, S. E.; Hottenga, J. J.; Jones, P. D.; Jousilahti, P.; Magi, R.; Medland, S. E.; Montgomery, G. W.; Nyholt, D. R.; Perola, M.; Pietilainen, K. H.; Salomaa, V.; Sillanpaa, E.; Suchiman, H. E.; van Heemst, D.; Willemsen, G.; Agudo, A.; Boeing, H.; Boomsma, D. I.; Chirlaque, M. D.; Fagherazzi, G.; Ferrari, P.; Franks, P.; Gieger, C.; Eriksson, J. G.; Gunter, M.; Hagg, S.; Hovatta, I.; Imaz, L.; Kaprio, J.; Kaaks, R.; Key, T.; Krogh, V.; Martin, N. G.; Melander, O.; Metspalu, A.; Moreno, C.; Onland-Moret, N. C.; Nilsson, P.; Ong, K. K.; Overvad, K.; Palli, D.; Panico, S.; Pedersen, N. L.; Penninx, Bwjh; Quiros, J. R.; Jarvelin, M. R.; Rodriguez-Barranco, M.; Scott, R. A.; Severi, G.; Slagboom, P. E.; Spector, T. D.; Tjonneland, A.; Trichopoulou, A.; Tumino, R.; Uitterlinden, A. G.; van der Schouw, Y. T.; van Duijn, C. M.; Weiderpass, E.; Denchi, E. L.; Matullo, G.; Butterworth, A. S.; Danesh, J.; Samani, N. J.; Wareham, N. J.; Nelson, C. P.; Langenberg, C.; Codd, V.

doi:10.1016/j.ajhg.2020.02.006

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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

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Deelen, J.
Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Slagboom, P. E.
Slagboom – Molecular Epidemiology, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/32109421
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Citation

Li, C., Stoma, S., Lotta, L. A., Warner, S., Albrecht, E., Allione, A., et al. (2020). Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length. Am J Hum Genet, 106(3), 389-404. doi:10.1016/j.ajhg.2020.02.006.

Cite as: https://hdl.handle.net/21.11116/0000-000B-308B-2

Abstract

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.