Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
Autor: | Joris Deelen, Antonia Trichopoulou, Sara Hägg, Kim Overvad, Elisabete Weiderpass, Iryna O. Fedko, Rudolf Kaaks, Nicola D. Kerrison, Kirsi H. Pietiläinen, Ida Surakka, Veikko Salomaa, Svetlana Stoma, Jaakko Kaprio, Alessandra Allione, Cornelia M. van Duijn, Nicholas G. Martin, Veryan Codd, Olle Melander, Nilesh J. Samani, Josine E. Verhoeven, Anne Tjønneland, Natalia Pervjakova, Domenico Palli, Adam S. Butterworth, Nicholas J. Wareham, María Dolores Chirlaque, P. Eline Slagboom, Massimo Mangino, Pascal P. Arp, Christopher P. Nelson, Brenda W.J.H. Penninx, Jessica L. Buxton, Pietro Ferrari, Tao Jiang, Iiris Hovatta, Taylor K. Loe, N. Charlotte Onland-Moret, Salvatore Panico, Peter Jones, Heiner Boeing, Timothy J. Key, Luca A. Lotta, Miguel Rodríguez-Barranco, Diana van Heemst, Chen Li, Robert A. Scott, Sarah E. Medland, Giuseppe Matullo, Alexessander Couto Alves, Rosario Tumino, Jouke-Jan Hottenga, Ken K. Ong, Vittorio Krogh, Gonneke Willemsen, Andres Metspalu, Eva Albrecht, Elina Sillanpää, Johan G. Eriksson, Najaf Amin, Dale R. Nyholt, Reedik Mägi, Eros Lazzerini Denchi, Peter M. Nilsson, André G. Uitterlinden, Antonio Agudo, Yuri Milaneschi, Ashley van der Spek, Alessia Russo, Linda Broer, Federico Canzian, Marian Beekman, Grant W. Montgomery, Sophie C Warner, Guy Fagherazzi, Markus Perola, Alexandra I. F. Blakemore, Marjo-Riitta Järvelin, Robert Karlsson, Tim D. Spector, Paul W. Franks, H. Eka D. Suchiman, Claudia Langenberg, Liher Imaz, Nancy L. Pedersen, Scott D. Gordon, Stephen E. Hamby, J. Ramón Quirós, Yvonne T. van der Schouw, Concha Moreno, Christian Gieger, Pekka Jousilahti, Dorret I. Boomsma, Marc J. Gunter, Benjamin Miraglio, Gianluca Severi, John Danesh |
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Přispěvatelé: | UNIVERSITY OF OULU, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, APH - Methodology, Sociology and Social Gerontology, Li, Chen [0000-0002-6423-6325], Ong, Kenneth [0000-0003-4689-7530], Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Apollo - University of Cambridge Repository, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Institute for Molecular Medicine Finland, University of Helsinki, Research Programs Unit, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, HUS Abdominal Center, Department of Medicine, Endokrinologian yksikkö, Clinicum, Diabetes and Obesity Research Program, Department of General Practice and Primary Health Care, HUS Helsinki and Uusimaa Hospital District, Department of Psychology and Logopedics, Genetics, SLEEPWELL Research Program, Department of Public Health, Mind and Matter, Internal Medicine, Epidemiology |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Netherlands Twin Register (NTR)
Limfomes LOCI Genome-wide association study Disease VARIANTS DISEASE 0302 clinical medicine Leukocytes telomere length GWAS Genetics(clinical) Càncer Mendelian randomisation Thyroid cancer Genetics (clinical) 11 Medical and Health Sciences Cancer Genetics Genetics & Heredity RISK 0303 health sciences Telòmer age-related disease biological aging Humans Nucleotides Genome-Wide Association Study Telomere meta-analyysi genomiikka Genomics CANCER 3. Good health 030220 oncology & carcinogenesis MENDELIAN RANDOMIZATION Medical genetics Biomarker (medicine) HEART Lymphomas Life Sciences & Biomedicine Medical Genetics medicine.medical_specialty GENES DATABASE Age-related Disease Biological Aging Mendelian Randomisation Telomere Length Biology Article 03 medical and health sciences SDG 3 - Good Health and Well-being Mendelian randomization medicine Journal Article 030304 developmental biology Medicinsk genetik Science & Technology 06 Biological Sciences medicine.disease Genòmica ikääntyminen 1182 Biochemistry cell and molecular biology telomeerit biological |
Zdroj: | American Journal of Human Genetics, 106(3), 389-404. CELL PRESS 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, 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, 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, ' Genome-Wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American Journal of Human Genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006 Am. J. Hum. Genet. 106, 389-404 (2020) American Journal of Human Genetics, 106(3), 389-404. Cell Press Dipòsit Digital de la UB Universidad de Barcelona Am J Hum Genet American journal of human genetics, 106(3), 389-404. Cell Press American Journal of Human Genetics 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, 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, 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, ' Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American journal of human genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006 American Journal of Human Genetics, 106(3), 389. Cell Press 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, 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, 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, ' Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American Journal of Human Genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006 |
ISSN: | 0002-9297 |
Popis: | 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. |
Databáze: | OpenAIRE |
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