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Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.
Taub, Margaret A; Conomos, Matthew P; Keener, Rebecca; Iyer, Kruthika R; Weinstock, Joshua S; Yanek, Lisa R; Lane, John; Miller-Fleming, Tyne W; Brody, Jennifer A; Raffield, Laura M; McHugh, Caitlin P; Jain, Deepti; Gogarten, Stephanie M; Laurie, Cecelia A; Keramati, Ali; Arvanitis, Marios; Smith, Albert V; Heavner, Benjamin; Barwick, Lucas; Becker, Lewis C; Bis, Joshua C; Blangero, John; Bleecker, Eugene R; Burchard, Esteban G; Celedón, Juan C; Chang, Yen Pei C; Custer, Brian; Darbar, Dawood; de Las Fuentes, Lisa; DeMeo, Dawn L; Freedman, Barry I; Garrett, Melanie E; Gladwin, Mark T; Heckbert, Susan R; Hidalgo, Bertha A; Irvin, Marguerite R; Islam, Talat; Johnson, W Craig; Kaab, Stefan; Launer, Lenore; Lee, Jiwon; Liu, Simin; Moscati, Arden; North, Kari E; Peyser, Patricia A; Rafaels, Nicholas; Seidman, Christine; Weeks, Daniel E; Wen, Fayun; Wheeler, Marsha M.
Afiliação
  • Taub MA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA.
  • Conomos MP; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Keener R; Department of Biomedical Engineering, Johns Hopkins Whiting School of Engineering, Baltimore, MD, USA.
  • Iyer KR; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA.
  • Weinstock JS; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Yanek LR; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Lane J; GeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine, Baltimore MD USA.
  • Miller-Fleming TW; Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, USA.
  • Brody JA; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Raffield LM; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • McHugh CP; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
  • Jain D; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Gogarten SM; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Laurie CA; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Keramati A; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Arvanitis M; Department of Cardiology, Johns Hopkins School of Medicine, Baltimore MD USA.
  • Smith AV; Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore MD USA.
  • Heavner B; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Barwick L; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Becker LC; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Bis JC; LTRC Data Coordinating Center, The Emmes Company, LLC, Rockville, MD, USA.
  • Blangero J; GeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine, Baltimore MD USA.
  • Bleecker ER; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Burchard EG; Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
  • Celedón JC; Department of Medicine, Division of Genetics, Genomics and Precision Medicine, University of Arizona, Tucson, AZ, USA.
  • Chang YPC; Division of Pharmacogenomics, University of Arizona, Tucson, AZ, USA.
  • Custer B; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Darbar D; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • de Las Fuentes L; Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.
  • DeMeo DL; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Freedman BI; Vitalant Research Institute, San Francisco, CA, USA.
  • Garrett ME; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Gladwin MT; Division of Cardiology, University of Illinois at Chicago, Chicago, IL, USA.
  • Heckbert SR; Cardiovascular Division, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Hidalgo BA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Irvin MR; Harvard Medical School, Boston, MA, USA.
  • Islam T; Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Johnson WC; Department of Medicine and Duke Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, NC, USA.
  • Kaab S; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
  • Launer L; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Lee J; Cardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Liu S; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
  • Moscati A; Department of Epidemiology, University of Alabama Birmingham, Birmingham, AL, USA.
  • North KE; Department of Epidemiology, University of Alabama Birmingham, Birmingham, AL, USA.
  • Peyser PA; Division of Environmental Health, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
  • Rafaels N; Department of Biostatistics, Collaborative Health Studies Coordinating Center, University of Washington, Seattle, WA, USA.
  • Seidman C; Department of Medicine I, University Hospital Munich, Ludwig-Maximilian's University, Munich, Germany.
  • Weeks DE; German Centre for Cardiovascular Research (DZHK); partner site: Munich Heart Alliance, Munich, Germany.
  • Wen F; Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Wheeler MM; Department of Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
Cell Genom ; 2(1)2022 Jan 12.
Article em En | MEDLINE | ID: mdl-35530816
ABSTRACT
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 populations. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Cell Genom Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Cell Genom Ano de publicação: 2022 Tipo de documento: Article