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Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.
He, Karen Y; Li, Xiaoyin; Kelly, Tanika N; Liang, Jingjing; Cade, Brian E; Assimes, Themistocles L; Becker, Lewis C; Beitelshees, Amber L; Bress, Adam P; Chang, Yen-Pei Christy; Chen, Yii-Der Ida; de Vries, Paul S; Fox, Ervin R; Franceschini, Nora; Furniss, Anna; Gao, Yan; Guo, Xiuqing; Haessler, Jeffrey; Hwang, Shih-Jen; Irvin, Marguerite Ryan; Kalyani, Rita R; Liu, Ching-Ti; Liu, Chunyu; Martin, Lisa Warsinger; Montasser, May E; Muntner, Paul M; Mwasongwe, Stanford; Palmas, Walter; Reiner, Alex P; Shimbo, Daichi; Smith, Jennifer A; Snively, Beverly M; Yanek, Lisa R; Boerwinkle, Eric; Correa, Adolfo; Cupples, L Adrienne; He, Jiang; Kardia, Sharon L R; Kooperberg, Charles; Mathias, Rasika A; Mitchell, Braxton D; Psaty, Bruce M; Vasan, Ramachandran S; Rao, D C; Rich, Stephen S; Rotter, Jerome I; Wilson, James G; Chakravarti, Aravinda; Morrison, Alanna C; Levy, Daniel.
Afiliação
  • He KY; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
  • Li X; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
  • Kelly TN; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, 70112, USA.
  • Liang J; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
  • Cade BE; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, 02115, USA.
  • Assimes TL; Division of Sleep Medicine, Harvard Medical School, Boston, MA, 02115, USA.
  • Becker LC; Department of Medicine, Stanford University, Palo Alto, CA, 94305, USA.
  • Beitelshees AL; GeneSTAR Research Program, Divisions of Cardiology and General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Bress AP; Program for Personalized and Genomic Medicine, Division of Endocrinology Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • Chang YC; Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
  • Chen YI; Program for Personalized and Genomic Medicine, Division of Endocrinology Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • de Vries PS; Departments of Pediatrics and Medicine, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
  • Fox ER; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Franceschini N; Division of Cardiovascular Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
  • Furniss A; Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC, 27599, USA.
  • Gao Y; Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
  • Guo X; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
  • Haessler J; Departments of Pediatrics and Medicine, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
  • Hwang SJ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • Irvin MR; Boston University's and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, 01702, USA.
  • Kalyani RR; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AB, 35294, USA.
  • Liu CT; GeneSTAR Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Liu C; Boston University's and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, 01702, USA.
  • Martin LW; Boston University's and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, 01702, USA.
  • Montasser ME; Division of Cardiology, Department of Medicine, George Washington University, Washington, DC, 20052, USA.
  • Muntner PM; Program for Personalized and Genomic Medicine, Division of Endocrinology Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • Mwasongwe S; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AB, 35294, USA.
  • Palmas W; Jackson Heart Study, Jackson State University, Jackson, MS, 39217, USA.
  • Reiner AP; Division of General Medicine, Columbia University Medical Center, New York, NY, 10032, USA.
  • Shimbo D; Department of Epidemiology, University of Washington, Seattle, WA, 98195, USA.
  • Smith JA; Division of General Medicine, Columbia University Medical Center, New York, NY, 10032, USA.
  • Snively BM; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Yanek LR; Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, 27101, USA.
  • Boerwinkle E; GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Correa A; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Cupples LA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • He J; Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
  • Kardia SLR; Boston University's and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, 01702, USA.
  • Kooperberg C; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, 70112, USA.
  • Mathias RA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Mitchell BD; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • Psaty BM; GeneSTAR Research Program, Divisions of Allergy and Clinical Immunology and General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Vasan RS; Program for Personalized and Genomic Medicine, Division of Endocrinology Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • Rao DC; Geriatrics Research and Education Clinical Center, Veterans Affairs Medical Center, Baltimore, MD, 21201, USA.
  • Rich SS; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, 98195, USA.
  • Rotter JI; Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
  • Wilson JG; Boston University's and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, 01702, USA.
  • Chakravarti A; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
  • Morrison AC; Departments of Pediatrics and Medicine, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
  • Levy D; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Hum Genet ; 138(2): 199-210, 2019 Feb.
Article em En | MEDLINE | ID: mdl-30671673
ABSTRACT
In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p < 0.05). One of the genes is RBFOX1, an evolutionarily conserved RNA-binding protein that regulates tissue-specific alternative splicing that we previously reported to be associated with BP using exome array data in CFS. After follow-up analysis of the 25 genes in ten independent TOPMed studies with individuals of European, African, and East Asian ancestry, and Hispanics (N = 29,988), we identified variants in SLX4 (p = 2.19 × 10-4) to be significantly associated with BP traits when accounting for multiple testing. We also replicated the associations previously reported for RBFOX1 (p = 0.007). Follow-up analysis with GTEx eQTL data shows SLX4 variants are associated with gene expression in coronary artery, multiple brain tissues, and right atrial appendage of the heart. Our study demonstrates that linkage analysis of family data can provide an efficient approach for detecting rare variants associated with complex traits in WGS data.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Pressão Sanguínea / Cromossomos Humanos Par 16 / Genoma Humano / Sequenciamento de Nucleotídeos em Larga Escala / Exoma / Ligação Genética Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Hum Genet Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Pressão Sanguínea / Cromossomos Humanos Par 16 / Genoma Humano / Sequenciamento de Nucleotídeos em Larga Escala / Exoma / Ligação Genética Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Hum Genet Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos