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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/173206
Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
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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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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 g., GUNTER, Marc j., 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 m., ONG, Ken k., OVERVAD, Kim, PALLI, Domenico, PANICO, Salvatore, PEDERSEN, Nancy l., PENNINX, Brenda w. j. h., QUIRÓS, José 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. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length. _American Journal of Human Genetics_. 2020. Vol. 106, núm. 3, pàgs. 389-404. [consulta: 8 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/173206]