6533b7dcfe1ef96bd1272187
RESEARCH PRODUCT
Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
Joris DeelenAntonia TrichopoulouSara HäggKim OvervadElisabete WeiderpassIryna O. FedkoRudolf KaaksNicola D. KerrisonKirsi H. PietiläinenIda SurakkaVeikko SalomaaSvetlana StomaJaakko KaprioAlessandra AllioneCornelia M. Van DuijnNicholas G. MartinVeryan CoddVeryan CoddOlle MelanderNilesh J. SamaniJosine E. VerhoevenAnne TjønnelandNatalia PervjakovaDomenico PalliAdam S. ButterworthNicholas J. WarehamMaría Dolores ChirlaqueP. Eline SlagboomMassimo ManginoPascal P. ArpChristopher P. NelsonBrenda W.j.h. PenninxJessica L. BuxtonPietro FerrariTao JiangIiris HovattaTaylor K. LoeN. Charlotte Onland-moretSalvatore PanicoPeter JonesHeiner BoeingTimothy J. KeyLuca A. LottaMiguel Rodríguez-barrancoDiana Van HeemstChen LiRobert A. ScottSarah E. MedlandGiuseppe MatulloAlexessander Couto AlvesRosario TuminoJouke-jan HottengaKen K. OngVittorio KroghGonneke WillemsenAndres MetspaluEva AlbrechtElina SillanpääJohan G. ErikssonNajaf AminDale R. NyholtReedik MägiEros Lazzerini DenchiPeter M. NilssonAndré G. UitterlindenAntonio AgudoYuri MilaneschiAshley Van Der SpekAlessia RussoLinda BroerFederico CanzianMarian BeekmanGrant W. MontgomerySophie C WarnerGuy FagherazziMarkus PerolaAlexandra I. F. BlakemoreMarjo-riitta JärvelinRobert KarlssonTim D. SpectorPaul W. FranksH. Eka D. SuchimanClaudia LangenbergLiher ImazNancy L. PedersenScott D. GordonStephen E. HambyJ. Ramón QuirósYvonne T. Van Der SchouwConcha MorenoChristian GiegerPekka JousilahtiDorret I. BoomsmaMarc J. GunterBenjamin MiraglioGianluca SeveriJohn Daneshsubject
Netherlands Twin Register (NTR)LimfomesLOCIGenome-wide association studyDiseaseVARIANTSDISEASE0302 clinical medicineLeukocytestelomere lengthGWASGenetics(clinical)CàncerMendelian randomisationThyroid cancerGenetics (clinical)11 Medical and Health SciencesCancerGeneticsGenetics & HeredityRISK0303 health sciencesTelòmerage-related disease; biological aging; Mendelian randomisation; telomere length; Humans; Leukocytes; Nucleotides; Genome-Wide Association Study; TelomereNucleotidesmeta-analyysigenomiikkaGenomicsTelomereCANCER3. Good health030220 oncology & carcinogenesisbiological agingMENDELIAN RANDOMIZATION/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingMedical geneticsBiomarker (medicine)HEARTLymphomasLife Sciences & BiomedicineMedical Geneticsmedicine.medical_specialtyGENESDATABASEAge-related Disease ; Biological Aging ; Mendelian Randomisation ; Telomere LengthBiologyArticle03 medical and health sciencesSDG 3 - Good Health and Well-beingMendelian randomization/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_medicineGeneticsJournal ArticleHumans030304 developmental biologyMedicinsk genetikage-related diseaseScience & TechnologyCancer06 Biological Sciencesmedicine.diseaseTelomereGenòmicaikääntyminen1182 Biochemistry cell and molecular biologytelomeeritbiologicalGenome-Wide Association Studydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-03-05 |