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Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.
Natarajan, Pradeep; Peloso, Gina M; Zekavat, Seyedeh Maryam; Montasser, May; Ganna, Andrea; Chaffin, Mark; Khera, Amit V; Zhou, Wei; Bloom, Jonathan M; Engreitz, Jesse M; Ernst, Jason; O'Connell, Jeffrey R; Ruotsalainen, Sanni E; Alver, Maris; Manichaikul, Ani; Johnson, W Craig; Perry, James A; Poterba, Timothy; Seed, Cotton; Surakka, Ida L; Esko, Tonu; Ripatti, Samuli; Salomaa, Veikko; Correa, Adolfo; Vasan, Ramachandran S; Kellis, Manolis; Neale, Benjamin M; Lander, Eric S; Abecasis, Goncalo; Mitchell, Braxton; Rich, Stephen S; Wilson, James G; Cupples, L Adrienne; Rotter, Jerome I; Willer, Cristen J; Kathiresan, Sekar.
Afiliação
  • Natarajan P; Center for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Peloso GM; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
  • Zekavat SM; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • Montasser M; Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
  • Ganna A; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • Chaffin M; Yale School of Medicine, New Haven, CT, 06510, USA.
  • Khera AV; Department of Computational Biology & Bioinformatics, Yale University, New Haven, CT, 06520, USA.
  • Zhou W; School of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
  • Bloom JM; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • Engreitz JM; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Ernst J; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • O'Connell JR; Center for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Ruotsalainen SE; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
  • Alver M; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • Manichaikul A; Department of Computational Medicine and Bioinformatics, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Johnson WC; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • Perry JA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Poterba T; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • Seed C; Society of Fellows, Harvard University, Cambridge, MA, 02138, USA.
  • Surakka IL; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • Esko T; School of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
  • Ripatti S; Institute for Molecular Medicine Finland, Helsinki, 00290, Finland.
  • Salomaa V; Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Correa A; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
  • Vasan RS; Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
  • Kellis M; School of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
  • Neale BM; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • Lander ES; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Abecasis G; Broad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
  • Mitchell B; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
  • Rich SS; Institute for Molecular Medicine Finland, Helsinki, 00290, Finland.
  • Wilson JG; Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Cupples LA; Institute for Molecular Medicine Finland, Helsinki, 00290, Finland.
  • Rotter JI; Institute for Molecular Medicine Finland, Helsinki, 00290, Finland.
  • Willer CJ; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
  • Kathiresan S; Sections of Preventive Medicine and Epidemiology and Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA.
Nat Commun ; 9(1): 3391, 2018 08 23.
Article em En | MEDLINE | ID: mdl-30140000
Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Humano / Sequenciamento de Nucleotídeos em Larga Escala / Lipídeos Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Humano / Sequenciamento de Nucleotídeos em Larga Escala / Lipídeos Idioma: En Ano de publicação: 2018 Tipo de documento: Article