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000154479 0247_ $$2doi$$a10.1016/j.ajhg.2020.02.006
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000154479 1001_ $$aLi, Chen$$b0
000154479 245__ $$aGenome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.
000154479 260__ $$aNew York, NY$$bElsevier$$c2020
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000154479 520__ $$aLeukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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000154479 7001_ $$aLotta, Luca A$$b2
000154479 7001_ $$aWarner, Sophie$$b3
000154479 7001_ $$aAlbrecht, Eva$$b4
000154479 7001_ $$aAllione, Alessandra$$b5
000154479 7001_ $$aArp, Pascal P$$b6
000154479 7001_ $$aBroer, Linda$$b7
000154479 7001_ $$aBuxton, Jessica L$$b8
000154479 7001_ $$aDa Silva Couto Alves, Alexessander$$b9
000154479 7001_ $$aDeelen, Joris$$b10
000154479 7001_ $$aFedko, Iryna O$$b11
000154479 7001_ $$aGordon, Scott D$$b12
000154479 7001_ $$aJiang, Tao$$b13
000154479 7001_ $$aKarlsson, Robert$$b14
000154479 7001_ $$aKerrison, Nicola$$b15
000154479 7001_ $$aLoe, Taylor K$$b16
000154479 7001_ $$aMangino, Massimo$$b17
000154479 7001_ $$aMilaneschi, Yuri$$b18
000154479 7001_ $$aMiraglio, Benjamin$$b19
000154479 7001_ $$aPervjakova, Natalia$$b20
000154479 7001_ $$aRusso, Alessia$$b21
000154479 7001_ $$aSurakka, Ida$$b22
000154479 7001_ $$avan der Spek, Ashley$$b23
000154479 7001_ $$aVerhoeven, Josine E$$b24
000154479 7001_ $$aAmin, Najaf$$b25
000154479 7001_ $$aBeekman, Marian$$b26
000154479 7001_ $$aBlakemore, Alexandra I$$b27
000154479 7001_ $$0P:(DE-He78)5323704270b6393dcea70186ffd86bca$$aCanzian, Federico$$b28$$udkfz
000154479 7001_ $$aHamby, Stephen E$$b29
000154479 7001_ $$aHottenga, Jouke-Jan$$b30
000154479 7001_ $$aJones, Peter D$$b31
000154479 7001_ $$aJousilahti, Pekka$$b32
000154479 7001_ $$aMägi, Reedik$$b33
000154479 7001_ $$aMedland, Sarah E$$b34
000154479 7001_ $$aMontgomery, Grant W$$b35
000154479 7001_ $$aNyholt, Dale R$$b36
000154479 7001_ $$aPerola, Markus$$b37
000154479 7001_ $$aPietiläinen, Kirsi H$$b38
000154479 7001_ $$aSalomaa, Veikko$$b39
000154479 7001_ $$aSillanpää, Elina$$b40
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000154479 7001_ $$avan Heemst, Diana$$b42
000154479 7001_ $$aWillemsen, Gonneke$$b43
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000154479 7001_ $$aBoomsma, Dorret I$$b46
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000154479 7001_ $$aFerrari, Pietro$$b49
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000154479 7001_ $$aMelander, Olle$$b62
000154479 7001_ $$aMetspalu, Andres$$b63
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000154479 7001_ $$aRodríguez-Barranco, Miguel$$b75
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000154479 7001_ $$aSeveri, Gianluca$$b77
000154479 7001_ $$aSlagboom, P Eline$$b78
000154479 7001_ $$aSpector, Tim D$$b79
000154479 7001_ $$aTjonneland, Anne$$b80
000154479 7001_ $$aTrichopoulou, Antonia$$b81
000154479 7001_ $$aTumino, Rosario$$b82
000154479 7001_ $$aUitterlinden, André G$$b83
000154479 7001_ $$avan der Schouw, Yvonne T$$b84
000154479 7001_ $$avan Duijn, Cornelia M$$b85
000154479 7001_ $$aWeiderpass, Elisabete$$b86
000154479 7001_ $$aDenchi, Eros Lazzerini$$b87
000154479 7001_ $$aMatullo, Giuseppe$$b88
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