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  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., 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.

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Li, C., Author
Stoma, S., Author
Lotta, L. A., Author
Warner, S., Author
Albrecht, E., Author
Allione, A., Author
Arp, P. P., Author
Broer, L., Author
Buxton, J. L., Author
Da Silva Couto Alves, A., Author
Deelen, J.1, Author           
Fedko, I. O., Author
Gordon, S. D., Author
Jiang, T., Author
Karlsson, R., Author
Kerrison, N., Author
Loe, T. K., Author
Mangino, M., Author
Milaneschi, Y., Author
Miraglio, B., Author
Pervjakova, N., AuthorRusso, A., AuthorSurakka, I., Authorvan der Spek, A., AuthorVerhoeven, J. E., AuthorAmin, N., AuthorBeekman, M., AuthorBlakemore, A. I., AuthorCanzian, F., AuthorHamby, S. E., AuthorHottenga, J. J., AuthorJones, P. D., AuthorJousilahti, P., AuthorMagi, R., AuthorMedland, S. E., AuthorMontgomery, G. W., AuthorNyholt, D. R., AuthorPerola, M., AuthorPietilainen, K. H., AuthorSalomaa, V., AuthorSillanpaa, E., AuthorSuchiman, H. E., Authorvan Heemst, D., AuthorWillemsen, G., AuthorAgudo, A., AuthorBoeing, H., AuthorBoomsma, D. I., AuthorChirlaque, M. D., AuthorFagherazzi, G., AuthorFerrari, P., AuthorFranks, P., AuthorGieger, C., AuthorEriksson, J. G., AuthorGunter, M., AuthorHagg, S., AuthorHovatta, I., AuthorImaz, L., AuthorKaprio, J., AuthorKaaks, R., AuthorKey, T., AuthorKrogh, V., AuthorMartin, N. G., AuthorMelander, O., AuthorMetspalu, A., AuthorMoreno, C., AuthorOnland-Moret, N. C., AuthorNilsson, P., AuthorOng, K. K., AuthorOvervad, K., AuthorPalli, D., AuthorPanico, S., AuthorPedersen, N. L., AuthorPenninx, Bwjh, AuthorQuiros, J. R., AuthorJarvelin, M. R., AuthorRodriguez-Barranco, M., AuthorScott, R. A., AuthorSeveri, G., AuthorSlagboom, P. E.2, Author           Spector, T. D., AuthorTjonneland, A., AuthorTrichopoulou, A., AuthorTumino, R., AuthorUitterlinden, A. G., Authorvan der Schouw, Y. T., Authorvan Duijn, C. M., AuthorWeiderpass, E., AuthorDenchi, E. L., AuthorMatullo, G., AuthorButterworth, A. S., AuthorDanesh, J., AuthorSamani, N. J., AuthorWareham, N. J., AuthorNelson, C. P., AuthorLangenberg, C., AuthorCodd, V., Author more..
Affiliations:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006              
2Slagboom – Molecular Epidemiology, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394013              

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Free keywords: Mendelian randomisation age-related disease biological aging telomere length
 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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 Dates: 2020-03-052020-02-29
 Publication Status: Issued
 Pages: -
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 Rev. Type: -
 Identifiers: Other: 32109421
DOI: 10.1016/j.ajhg.2020.02.006
ISSN: 1537-6605 (Electronic)0002-9297 (Linking)
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Title: Am J Hum Genet
Source Genre: Journal
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Pages: - Volume / Issue: 106 (3) Sequence Number: - Start / End Page: 389 - 404 Identifier: -