Journal Article

DKFZ-2020-00801

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.DKFZ* ; Hamby, S. E. ; Hottenga, J.-J. ; Jones, P. D. ; Jousilahti, P. ; Mägi, R. ; Medland, S. E. ; Montgomery, G. W. ; Nyholt, D. R. ; Perola, M. ; Pietiläinen, K. H. ; Salomaa, V. ; Sillanpää, 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. ; Hägg, S. ; Hovatta, I. ; Imaz, L. ; Kaprio, J. ; Kaaks, R.DKFZ* ; 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, B. W. J. H. ; Quirós, J. R. ; Jarvelin, M. R. ; Rodríguez-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.

2020
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.ajhg.2020.02.006

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.

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Contributing Institute(s):

1. C055 Genomische Epidemiologie (C055)
2. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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