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The impact of low-frequency and rare variants on lipid levels.
Surakka, Ida; Horikoshi, Momoko; Mägi, Reedik; Sarin, Antti-Pekka; Mahajan, Anubha; Lagou, Vasiliki; Marullo, Letizia; Ferreira, Teresa; Miraglio, Benjamin; Timonen, Sanna; Kettunen, Johannes; Pirinen, Matti; Karjalainen, Juha; Thorleifsson, Gudmar; Hägg, Sara; Hottenga, Jouke-Jan; Isaacs, Aaron; Ladenvall, Claes; Beekman, Marian; Esko, Tõnu; Ried, Janina S; Nelson, Christopher P; Willenborg, Christina; Gustafsson, Stefan; Westra, Harm-Jan; Blades, Matthew; de Craen, Anton J M; de Geus, Eco J; Deelen, Joris; Grallert, Harald; Hamsten, Anders; Havulinna, Aki S; Hengstenberg, Christian; Houwing-Duistermaat, Jeanine J; Hyppönen, Elina; Karssen, Lennart C; Lehtimäki, Terho; Lyssenko, Valeriya; Magnusson, Patrik K E; Mihailov, Evelin; Müller-Nurasyid, Martina; Mpindi, John-Patrick; Pedersen, Nancy L; Penninx, Brenda W J H; Perola, Markus; Pers, Tune H; Peters, Annette; Rung, Johan; Smit, Johannes H; Steinthorsdottir, Valgerdur.
Afiliação
  • Surakka I; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare, Helsinki, Finland.
  • Horikoshi M; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
  • Mägi R; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Sarin AP; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare, Helsinki, Finland.
  • Mahajan A; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Lagou V; 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
  • Marullo L; Department of Life Sciences and Biotechnology, Genetic Section, University of Ferrara, Ferrara, Italy.
  • Ferreira T; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Miraglio B; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Timonen S; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Kettunen J; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare, Helsinki, Finland.
  • Pirinen M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Karjalainen J; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Thorleifsson G; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
  • Hägg S; 1] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [2] Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. [3] Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Hottenga JJ; Department of Biological Psychology, EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam, the Netherlands.
  • Isaacs A; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. [2] Centre for Medical Systems Biology, Leiden, the Netherlands.
  • Ladenvall C; Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
  • Beekman M; 1] Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. [2] Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
  • Esko T; 1] Estonian Genome Center, University of Tartu, Tartu, Estonia. [2] Division of Endocrinology, Children's Hospital, Boston, Massachusetts, USA. [3] Center for Basic and Translational Obesity Research, Children's Hospital, Boston, Massachusetts, USA. [4] Program in Medical and Population Genetics, Br
  • Ried JS; Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Nelson CP; 1] Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research (NIHR) Leicester Cardiovascular Disease Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
  • Willenborg C; 1] Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany. [2] Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), partner site Hamburg, Lübeck and Kiel, Germany.
  • Gustafsson S; 1] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [2] Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. [3] Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Westra HJ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Blades M; Department of Epidemiology and Biostatistics, Medical Research Council (MRC) Health Protection Agency (HPA), Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • de Craen AJ; 1] Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. [2] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
  • de Geus EJ; Department of Biological Psychology, EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam, the Netherlands.
  • Deelen J; 1] Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. [2] Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
  • Grallert H; 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [2] German Center for Diabetes Research (DZD), Neuherberg, Germany. [3] Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Envir
  • Hamsten A; Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • Havulinna AS; National Institute for Health and Welfare, Helsinki, Finland.
  • Hengstenberg C; 1] Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. [2] Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), partner site Munich Heart Alliance, Munich, Germany.
  • Houwing-Duistermaat JJ; Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
  • Hyppönen E; 1] Population, Policy and Practice, University College London Institute of Child Health, London, UK. [2] South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. [3] School of Population Health, University of South Australia, Adelaide, South Australia, Australia.
  • Karssen LC; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Lehtimäki T; Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
  • Lyssenko V; 1] Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden. [2] Steno Diabetes Center, Gentofte, Denmark.
  • Magnusson PK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Mihailov E; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Müller-Nurasyid M; 1] Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [2] Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), partner site Munich Heart Alliance, Munich, Germany. [3] Department of Medicine I, University Hospital Groß
  • Mpindi JP; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Pedersen NL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Penninx BW; Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
  • Perola M; 1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare, Helsinki, Finland. [3] Estonian Genome Center, University of Tartu, Tartu, Estonia. [4] Diabetes and Obesity Research Program, University of Helsinki, Helsink
  • Pers TH; 1] Division of Endocrinology, Children's Hospital, Boston, Massachusetts, USA. [2] Center for Basic and Translational Obesity Research, Children's Hospital, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Peters A; 1] Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [2] Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [3] Deutsches Herzzentrum Münc
  • Rung J; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • Smit JH; Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
  • Steinthorsdottir V; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Nat Genet ; 47(6): 589-97, 2015 Jun.
Article em En | MEDLINE | ID: mdl-25961943
ABSTRACT
Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metabolismo dos Lipídeos Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Finlândia
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Metabolismo dos Lipídeos Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Finlândia