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

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...

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Detalles Bibliográficos
Autores principales: Li, Chen, Stoma, Svetlana, Lotta, Luca A., Warner, Sophie, Albrecht, Eva, Allione, Alessandra, Arp, Pascal P., Broer, Linda, Buxton, Jessica L., Da Silva Couto Alves, Alexessander, 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, Mägi, Reedik, Medland, Sarah E., Montgomery, Grant W., Nyholt, Dale R., Perola, Markus, Pietiläinen, Kirsi H., Salomaa, Veikko, Sillanpää, Elina, Suchiman, H. Eka, van Heemst, Diana, Willemsen, Gonneke, Agudo, Antonio, Boeing, Heiner, Boomsma, Dorret I., Chirlaque, Maria-Dolores, Fagherazzi, Guy, Ferrari, Pietro, Franks, Paul, Gieger, Christian, Eriksson, Johan Gunnar, Gunter, Marc, Hägg, 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., Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Uitterlinden, André G., van der Schouw, Yvonne T., van Duijn, Cornelia M., 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058826/
https://www.ncbi.nlm.nih.gov/pubmed/32109421
http://dx.doi.org/10.1016/j.ajhg.2020.02.006
Descripción
Sumario: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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