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Title: Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
Author: Li, Chen
Stoma, Svetlana
Lotta, Luca A.
Warner, Sophie
Albrecht, Eva
Allione, Alessandra
Arp, Pascal P.
Broer, Linda
Buxton, Jessica L.
Couto Alves, Alexessander Da Silva
Deelen, Joris
Fedko, Iryna O.
Gordon, Scott D.
Jiang, Tao
Karlsson, Robert
Kerrison, Nicola
Loe, Taylor K.
Mangino, Massimo
Milaneschi, Yuri
Miraglio, Benjamin
Pervjakova, Natalia
Russo, Alessia
Surakka, Ida
van der Spek, Ashley
Verhoeven, Josine E.
Amin, Najaf
Beekman, Marian
Blakemore, Alexandra I.
Canzian, Federico
Hamby, Stephen E.
Hottenga, Jouke-Jan
Jones, Peter D.
Jousilahti, Pekka
Magi, Reedik
Medland, Sarah E.
Montgomery, Grant W.
Nyholt, Dale R.
Perola, Markus
Pietilainen, Kirsi H.
Salomaa, Veikko
Sillanpaa, Elina
Suchiman, H. Eka
van Heemst, Diana
Willemsen, Gonneke
Agudo, Antonio
Boeing, Heiner
Boomsma, Dorret I.
Chirlaque, María Dolores
Fagherazzi, Guy
Ferrari, Pietro
Franks, Pau
Gieger, Christian
Eriksson, Johan Gunnar
Gunter, Marc
Hagg, Sara
Hovatta, Iiris
Imaz, Liher
Kaprio, Jaakko
Kaaks, Rudolf
Key, Timothy
Krogh, Vittorio
Martin, Nicholas G.
Melander, Olle
Metspalu, Andres
Moreno, Concha
Onland-Moret, N. Charlotte
Nilsson, Peter
Ong, Ken K.
Overvad, Kim
Palli, Domenico
Panico, Salvatore
Pedersen, Nancy L.
Penninx, Brenda W. J. H.
Quirós, J. Ramón
Jarvelin, Marjo Riitta
Rodríguez Barranco, Miguel
Scott, Robert A.
Severi, Gianluca
Slagboom, P. Eline
Spector, Tim D.
Tjønneland, Anne
Trichopoulou, Antonia
Tumino, Rosario
Uitterlinden, André G.
van der Schouw, Yvonne T.
van Duijn, Cornelia
Weiderpass, Elisabete
Denchi, Eros Lazzerini
Matullo, Giuseppe
Butterworth, Adam S.
Danesh, John
Samani, Nilesh J.
Wareham, Nicholas J.
Nelson, Christopher P.
Langenberg, Claudia
Codd, Veryan
Keywords: Telòmer
Issue Date: 1-Jan-2020
Publisher: Cell Press
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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It is part of: American Journal of Human Genetics, 2020, vol. 106, num. 3, p. 389-404
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Appears in Collections:Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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