biostudies-literatureTaub MABLRD VANCATS NIH HHSNICHD NIH HHSNCRR NIH HHSNIA NIH HHSNIEHS NIH HHSNIAID NIH HHSNHLBI NIH HHSNIDDK NIH HHSNHGRI NIH HHSNCI NIH HHSNINDS NIH HHSNIAMS NIH HHSNIH HHSNIGMS NIH HHSS2666-979X(21)00105-1https://www.ebi.ac.uk/biostudies/studies/S-EPMC9075703biostudies-literatureUnknown2(1)Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10^-9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across Cell genomicsGenetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.PMC9075703R01 HL132523R37 HL066289R01 HL143818UG1 HL139054RC2 GM092618R01 HL071205R01 HL113323R01 HL092301R01 HL113326R01 HL056177R01 HL117004U01 HL089897R01 HL068959U01 HL065962OT3 HL142481UM1 HL098123R01 HL067348U01 HL072496P01 AI148104OT3 HL142480UM1 HL128711R01 DK113003U01 HG004798R01 HL133221R01 HL120393R01 HL071051HHSN268200800007CR01 NS032830U10 HL064295R01 HL121007UH3 OD023282U01 HL072524R01 HL104608R01 HL112064U10 HL098112R01 HL095080R01 ES021801U01 HL157004UM1 HL098147R01 HL093093U01 HL080295R01 HL117626R03 HL154284P30 AG028747R01 HL111249R01 AR048797N01 HC025195UL1 RR024975R01 HL113264R01 DK071891P01 HL045522R01 HL080467S10 RR025141I01 BX005295UL1 TR002243U01 HL054457R01 HL079915R01 HL073410R01 HL097163OT3 HL142478R01 HL118267OT3 HL142479P50 GM115305R01 HL068986R25 GM062459U01 HL130114U10 HL064307R01 AG058921N01 HC085083N01 HC085082R01 HL104135N01 HC085081HHSN268201500014CU01 HL054464N01 HC085086U10 HL064305N01 HC085080R01 HL055673R01 HL090682R01 HL089856R01 HL080083R01 HL091889R01 HL092217R01 HL066216U01 HL089856R01 HL141845T32 HG000040R01 HL085251U01 HL117721UM1 HL098162K01 HL135405R01 HL071259UH3 HL151865R01 HL07125875N92021D00006U01 HG006378S10 OD017985UL1 TR000445R01 HL092577R01 HL071250HHSN268201800001CU01 AI126614R01 HL087660U01 HL054472UM1 HG008895R01 HL087263U19 HL065962P01 ES011627U10 HL064288U01 HL054527UM1 HL128761U10 HL064287U01 HL072518HHSN268201200036CR01 HL119443U01 HL054481R01 HL046380U01 HL130045OT3 HL147154R01 HL087698R01 HL157635R01 NS058700U10 HL064313N01 HC095159R01 HL113338U01 HL072507R35 HL135818UG3 OD023282RC1 HL099355N01 HC085079U10 HL109164R01 HD074711R01 HL133040U19 CA203654R01 HL069234U10 HL054472Cupples LAYang IVSchwartz DAPsaty BMPankratz NBowden DWBurchard EGDarbar DGuo XSinner MFThornton TLane JTaylor JGSheu WHWiggins KLde las Fuentes LTOPMed Hematology and Hemostasis Working GroupTracy RPTiwari HKReupena MSNekhai SLoos RJHe JGarrett MEBattle AEllinor PTJain DLevin AMRedline SWilliams LKFingerlin TEShoemaker MBTaub MASciurba FLevy DMiller-Fleming TWJohnsen JMYanek LRBecker LCIrvin MRKelly SKardia SLMak ACLee JZhao WBlangero JCorrea ANaseri TSilverman EKMontgomery CGHwang SJConomos MPMinster RLGogarten SMSeidman CCox NJRaby BANHLBI CARE Networkde Andrade MSmith AVSabino ECSmith JATaylor KDKaplan RReiner APMcHugh CPArvanitis MBlackwell TWSu JLLaurie CCNouraie MLaurie CAMeyers DAHeckbert SRRoden DPalmer NDBis JCCeledon JCMathias RACuster BKooperberg CAviv AHidalgo BATOPMed Structural Variation Working GroupLauner LMitchell BDMcGarvey STRotter JIBoerwinkle ERich SSIyer KRWeinstock JSKumar RWilson JGRafaels NChen ZCurran JEBarwick LTelen MJGui HEng CWen FAbecasis GAuer PLVasan RSKeener RRaffield LMGilliland FDFreedman BIKenny EEWeeks DECho MHChang YPCBrody JAO'Connell JPeyser PAAslibekyan SGelb BDFornage MDeMeo DLPeralta JMKeramati AHeavner BIslam TAshley-Koch AEMoscati ADaya MLiu SSmith NLWeiss STWhite MJRuczinski IGladwin MTArnett DKArmanios MJohnson WCDeka RBleecker ERWheeler MMPerry JANickerson DAHou LCade BEKaab SZhang YKonkle BANHLBI Trans-Omics for Precision Medicine (TOPMed) ConsortiumChen YIBarnes KCLiu CNorth KEfalseGenetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10^-9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across 2022-01-01T00:00:00Z2022 Jan2026-05-09T19:46:47.148Z2025-08-18T09:53:23.733ZS-EPMC90757033553081610.1016/j.xgen.2021.100084