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

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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

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.; 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
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Research Programs Unit
University of Helsinki, HUS Abdominal Center
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, International Agency for Research on Cancer
Date: 2020-03-05
Language: eng
Number of pages: 16
Belongs to series: American Journal of Human Genetics
ISSN: 0002-9297
URI: http://hdl.handle.net/10138/313683
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.
Subject: 1182 Biochemistry, cell and molecular biology
telomere length
biological aging
Mendelian randomisation
age-related disease
GWAS
VARIANTS
RISK
LOCI
MENDELIAN RANDOMIZATION
CANCER
HEART
DATABASE
DISEASE
GENES
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