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

Li, Chen (author)
University of Cambridge,Glenfield Hospital
Stoma, Svetlana (author)
Karolinska Institutet
Lotta, Luca A. (author)
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Warner, Sophie (author)
Albrecht, Eva (author)
Allione, Alessandra (author)
Arp, Pascal P. (author)
Broer, Linda (author)
Buxton, Jessica L. (author)
Da Silva Couto Alves, Alexessander (author)
Deelen, Joris (author)
Fedko, Iryna O. (author)
Gordon, Scott D. (author)
Jiang, Tao (author)
Karlsson, Robert (author)
Karolinska Institutet
Kerrison, Nicola (author)
Loe, Taylor K. (author)
Mangino, Massimo (author)
Milaneschi, Yuri (author)
Miraglio, Benjamin (author)
Pervjakova, Natalia (author)
Russo, Alessia (author)
Surakka, Ida (author)
van der Spek, Ashley (author)
Verhoeven, Josine E. (author)
Amin, Najaf (author)
Beekman, Marian (author)
Blakemore, Alexandra I. (author)
Canzian, Federico (author)
Hamby, Stephen E. (author)
Hottenga, Jouke-Jan (author)
Jones, Peter D. (author)
Jousilahti, Pekka (author)
Mägi, Reedik (author)
Medland, Sarah E. (author)
Montgomery, Grant W. (author)
Nyholt, Dale R. (author)
Perola, Markus (author)
University of Helsinki,Finnish National Institute for Health and Welfare
Pietiläinen, Kirsi H. (author)
Salomaa, Veikko (author)
Sillanpää, Elina (author)
Suchiman, H. Eka (author)
van Heemst, Diana (author)
Willemsen, Gonneke (author)
Agudo, Antonio (author)
Boeing, Heiner (author)
Boomsma, Dorret I. (author)
Chirlaque, Maria-Dolores (author)
Fagherazzi, Guy (author)
Ferrari, Pietro (author)
Franks, Paul W. (author)
Umeå University,Lund University,Lunds universitet,Umeå universitet,Näringsforskning,Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, 20502 Malmö Sweden,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Gieger, Christian (author)
Eriksson, Johan Gunnar (author)
Helsinki University Central Hospital,University of Helsinki,National University of Singapore
Gunter, Marc (author)
Hagg, Sara (author)
Hovatta, Iiris (author)
Imaz, Liher (author)
Kaprio, Jaakko (author)
Kaaks, Rudolf (author)
Key, Timothy (author)
Krogh, Vittorio (author)
Martin, Nicholas G. (author)
Melander, Olle (author)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
Metspalu, Andres (author)
Moreno, Concha (author)
Onland-Moret, N. Charlotte (author)
Nilsson, Peter (author)
Skåne University Hospital
Ong, Ken K. (author)
Overvad, Kim (author)
Palli, Domenico (author)
Panico, Salvatore (author)
Pedersen, Nancy L. (author)
Karolinska Institutet
Penninx, Brenda W. J. H. (author)
Quirós, J. Ramón (author)
Riitta Jarvelin, Marjo (author)
Rodríguez-Barranco, Miguel (author)
Scott, Robert A. (author)
Severi, Gianluca (author)
Slagboom, P. Eline (author)
Spector, Tim D. (author)
Tjonneland, Anne (author)
Trichopoulou, Antonia (author)
Tumino, Rosario (author)
Uitterlinden, André G. (author)
van der Schouw, Yvonne T. (author)
van Duijn, Cornelia M. (author)
Weiderpass, Elisabete (author)
Denchi, Eros Lazzerini (author)
Matullo, Giuseppe (author)
Butterworth, Adam S. (author)
Danesh, John (author)
Samani, Nilesh J. (author)
Wareham, Nicholas J. (author)
Nelson, Christopher P. (author)
Langenberg, Claudia (author)
Codd, Veryan (author)
University of Leicester,Glenfield Hospital
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 (creator_code:org_t)
CELL PRESS, 2020
2020
English.
In: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 106:3, s. 389-404
  • Journal article (peer-reviewed)
Abstract Subject headings
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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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Keyword

telomere length
biological aging
Mendelian randomisation
age-related disease
age-related disease
biological aging
Mendelian randomisation
telomere length

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor
Li, Chen
Stoma, Svetlana
Lotta, Luca A.
Warner, Sophie
Albrecht, Eva
Allione, Alessan ...
show more...
Arp, Pascal P.
Broer, Linda
Buxton, Jessica ...
Da Silva Couto A ...
Deelen, Joris
Fedko, Iryna O.
Gordon, Scott D.
Jiang, Tao
Karlsson, Robert
Kerrison, Nicola
Loe, Taylor K.
Mangino, Massimo
Milaneschi, Yuri
Miraglio, Benjam ...
Pervjakova, Nata ...
Russo, Alessia
Surakka, Ida
van der Spek, As ...
Verhoeven, Josin ...
Amin, Najaf
Beekman, Marian
Blakemore, Alexa ...
Canzian, Federic ...
Hamby, Stephen E ...
Hottenga, Jouke- ...
Jones, Peter D.
Jousilahti, Pekk ...
Mägi, Reedik
Medland, Sarah E ...
Montgomery, Gran ...
Nyholt, Dale R.
Perola, Markus
Pietiläinen, Kir ...
Salomaa, Veikko
Sillanpää, Elina
Suchiman, H. Eka
van Heemst, Dian ...
Willemsen, Gonne ...
Agudo, Antonio
Boeing, Heiner
Boomsma, Dorret ...
Chirlaque, Maria ...
Fagherazzi, Guy
Ferrari, Pietro
Franks, Paul W.
Gieger, Christia ...
Eriksson, Johan ...
Gunter, Marc
Hagg, Sara
Hovatta, Iiris
Imaz, Liher
Kaprio, Jaakko
Kaaks, Rudolf
Key, Timothy
Krogh, Vittorio
Martin, Nicholas ...
Melander, Olle
Metspalu, Andres
Moreno, Concha
Onland-Moret, N. ...
Nilsson, Peter
Ong, Ken K.
Overvad, Kim
Palli, Domenico
Panico, Salvator ...
Pedersen, Nancy ...
Penninx, Brenda ...
Quirós, J. Ramón
Riitta Jarvelin, ...
Rodríguez-Barran ...
Scott, Robert A.
Severi, Gianluca
Slagboom, P. Eli ...
Spector, Tim D.
Tjonneland, Anne
Trichopoulou, An ...
Tumino, Rosario
Uitterlinden, An ...
van der Schouw, ...
van Duijn, Corne ...
Weiderpass, Elis ...
Denchi, Eros Laz ...
Matullo, Giusepp ...
Butterworth, Ada ...
Danesh, John
Samani, Nilesh J ...
Wareham, Nichola ...
Nelson, Christop ...
Langenberg, Clau ...
Codd, Veryan
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
Articles in the publication
American Journal ...
By the university
Umeå University
Lund University
Karolinska Institutet

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