TY  - JOUR
AU  - Li, Chen
AU  - Stoma, Svetlana
AU  - Lotta, Luca A
AU  - Warner, Sophie
AU  - Albrecht, Eva
AU  - Allione, Alessandra
AU  - Arp, Pascal P
AU  - Broer, Linda
AU  - Buxton, Jessica L
AU  - Da Silva Couto Alves, Alexessander
AU  - Deelen, Joris
AU  - Fedko, Iryna O
AU  - Gordon, Scott D
AU  - Jiang, Tao
AU  - Karlsson, Robert
AU  - Kerrison, Nicola
AU  - Loe, Taylor K
AU  - Mangino, Massimo
AU  - Milaneschi, Yuri
AU  - Miraglio, Benjamin
AU  - Pervjakova, Natalia
AU  - Russo, Alessia
AU  - Surakka, Ida
AU  - van der Spek, Ashley
AU  - Verhoeven, Josine E
AU  - Amin, Najaf
AU  - Beekman, Marian
AU  - Blakemore, Alexandra I
AU  - Canzian, Federico
AU  - Hamby, Stephen E
AU  - Hottenga, Jouke-Jan
AU  - Jones, Peter D
AU  - Jousilahti, Pekka
AU  - Mägi, Reedik
AU  - Medland, Sarah E
AU  - Montgomery, Grant W
AU  - Nyholt, Dale R
AU  - Perola, Markus
AU  - Pietiläinen, Kirsi H
AU  - Salomaa, Veikko
AU  - Sillanpää, Elina
AU  - Suchiman, H Eka
AU  - van Heemst, Diana
AU  - Willemsen, Gonneke
AU  - Agudo, Antonio
AU  - Boeing, Heiner
AU  - Boomsma, Dorret I
AU  - Chirlaque, Maria-Dolores
AU  - Fagherazzi, Guy
AU  - Ferrari, Pietro
AU  - Franks, Paul
AU  - Gieger, Christian
AU  - Eriksson, Johan Gunnar
AU  - Gunter, Marc
AU  - Hägg, Sara
AU  - Hovatta, Iiris
AU  - Imaz, Liher
AU  - Kaprio, Jaakko
AU  - Kaaks, Rudolf
AU  - Key, Timothy
AU  - Krogh, Vittorio
AU  - Martin, Nicholas G
AU  - Melander, Olle
AU  - Metspalu, Andres
AU  - Moreno, Concha
AU  - Onland-Moret, N Charlotte
AU  - Nilsson, Peter
AU  - Ong, Ken K
AU  - Overvad, Kim
AU  - Palli, Domenico
AU  - Panico, Salvatore
AU  - Pedersen, Nancy L
AU  - Penninx, Brenda W J H
AU  - Quirós, J Ramón
AU  - Jarvelin, Marjo Riitta
AU  - Rodríguez-Barranco, Miguel
AU  - Scott, Robert A
AU  - Severi, Gianluca
AU  - Slagboom, P Eline
AU  - Spector, Tim D
AU  - Tjonneland, Anne
AU  - Trichopoulou, Antonia
AU  - Tumino, Rosario
AU  - Uitterlinden, André G
AU  - van der Schouw, Yvonne T
AU  - van Duijn, Cornelia M
AU  - Weiderpass, Elisabete
AU  - Denchi, Eros Lazzerini
AU  - Matullo, Giuseppe
AU  - Butterworth, Adam S
AU  - Danesh, John
AU  - Samani, Nilesh J
AU  - Wareham, Nicholas J
AU  - Nelson, Christopher P
AU  - Langenberg, Claudia
AU  - Codd, Veryan
TI  - Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.
JO  - The American journal of human genetics
VL  - 106
IS  - 3
SN  - 0002-9297
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2020-00801
SP  - 389 - 404
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:32109421
C2  - pmc:PMC7058826
DO  - DOI:10.1016/j.ajhg.2020.02.006
UR  - https://inrepo02.dkfz.de/record/154479
ER  -