Evidence map›Paper›PMID 25961943›Full record

ArticleNature genetics2015

The impact of low-frequency and rare variants on lipid levels.

Ida Surakka, Momoko Horikoshi, Reedik Mägi, Antti-Pekka Sarin, Anubha Mahajan, Vasiliki Lagou, Letizia Marullo, Teresa Ferreira, Benjamin Miraglio, Sanna Timonen and 77 more

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In one paragraph

Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
227citing papers in PubMed, 18 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

227 citing papers in PubMed, 18 syntheses or guidelines pooled it.

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167 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

87 authors.

Ida Surakka1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare, Helsinki, Finland.
Momoko Horikoshi1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Reedik MägiEstonian Genome Center, University of Tartu, Tartu, Estonia.
Antti-Pekka Sarin1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare, Helsinki, Finland.
Anubha MahajanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Vasiliki Lagou1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Letizia MarulloDepartment of Life Sciences and Biotechnology, Genetic Section, University of Ferrara, Ferrara, Italy.
Teresa FerreiraWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Benjamin MiraglioInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Sanna TimonenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Johannes Kettunen1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare, Helsinki, Finland.
Matti PirinenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Juha KarjalainenDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Gudmar ThorleifssondeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Sara Hägg1] 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.
Jouke-Jan HottengaDepartment of Biological Psychology, EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam, the Netherlands.
Aaron Isaacs1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. [2] Centre for Medical Systems Biology, Leiden, the Netherlands.
Claes LadenvallDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
Marian Beekman1] Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. [2] Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
Tõnu Esko1] 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, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [5] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000000319826569
Janina S RiedInstitute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Christopher P Nelson1] 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.
Christina Willenborg1] 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.
Stefan Gustafsson1] 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.ORCID 0000000158940351
Harm-Jan WestraDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Matthew BladesDepartment 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.
Anton J M de Craen1] Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. [2] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Eco J de GeusDepartment of Biological Psychology, EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam, the Netherlands.ORCID 0000000160222666
Joris Deelen1] Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. [2] Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
Harald Grallert1] 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 Environmental Health, Neuherberg, Germany.
Anders HamstenCardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Aki S HavulinnaNational Institute for Health and Welfare, Helsinki, Finland.
Christian Hengstenberg1] Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. [2] Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), partner site Munich Heart Alliance, Munich, Germany.
Jeanine J Houwing-DuistermaatDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Elina Hyppönen1] 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. [4] Sansom Institute, University of South Australia, Adelaide, South Australia, Australia.
Lennart C KarssenGenetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID 000000021959342X
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
Valeriya Lyssenko1] Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden. [2] Steno Diabetes Center, Gentofte, Denmark.
Patrik K E MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Evelin MihailovEstonian Genome Center, University of Tartu, Tartu, Estonia.
Martina Müller-Nurasyid1] 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 Großhadern, Ludwig Maximilians Universität, Munich, Germany. [4] Chair of Genetic Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians Universität, Munich, Germany.
John-Patrick MpindiInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Nancy L PedersenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Brenda W J H PenninxDepartment of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
Markus Perola1] 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, Helsinki, Finland.
Tune H Pers1] 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.
Annette Peters1] 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 München, Technische Universität München, Munich, Germany.
Johan RungEuropean Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Johannes H SmitDepartment of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
Valgerdur SteinthorsdottirdeCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
Martin D TobinGenetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
Natalia TsernikovaEstonian Genome Center, University of Tartu, Tartu, Estonia.
Elisabeth M van LeeuwenGenetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Jorma S Viikari1] Department of Medicine, University of Turku, Turku, Finland. [2] Division of Medicine, Turku University Hospital, Turku, Finland.
Sara M WillemsGenetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Gonneke WillemsenDepartment of Biological Psychology, EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam, the Netherlands.
Heribert Schunkert1] Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. [2] Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), partner site Munich Heart Alliance, Munich, Germany.
Jeanette Erdmann1] 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.
Nilesh J Samani1] 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.
Jaakko Kaprio1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] National Institute for Health and Welfare, Helsinki, Finland. [3] Department of Public Health, University of Helsinki, Helsinki, Finland.ORCID 0000000237162455
Lars LindDepartment of Medical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.
Christian Gieger1] Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [2] Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. [3] Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Andres Metspalu1] Estonian Genome Center, University of Tartu, Tartu, Estonia. [2] Institute of Molecular and Cell Biology of the University of Tartu, Tartu, Estonia.
P Eline Slagboom1] Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. [2] Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
Leif Groop1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
Cornelia M van Duijn1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. [2] Centre for Medical Systems Biology, Leiden, the Netherlands.
Johan G Eriksson1] National Institute for Health and Welfare, Helsinki, Finland. [2] Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland. [3] Folkhälsan Research Centre, Helsinki, Finland. [4] Unit of Primary Health Care, Helsinki University Hospital, Helsinki, Finland.
Antti JulaNational Institute for Health and Welfare, Helsinki, Finland.
Veikko SalomaaNational Institute for Health and Welfare, Helsinki, Finland.
Dorret I BoomsmaDepartment of Biological Psychology, EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam, the Netherlands.
Christine PowerPopulation, Policy and Practice, University College London Institute of Child Health, London, UK.
Olli T Raitakari1] Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. [2] Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.
Erik Ingelsson1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. [3] Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Marjo-Riitta Järvelin1] National Institute for Health and Welfare, Helsinki, Finland. [2] [3] Institute of Health Sciences, University of Oulu, Oulu, Finland. [4] Biocenter Oulu, University of Oulu, Oulu, Finland. [5] Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
Unnur Thorsteinsdottir1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Lude FrankeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID 0000000251598802
Elina Ikonen1] Anatomy, Institute of Biomedicine, University of Helsinki, Helsinki, Finland. [2] Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Olli KallioniemiInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.ORCID 0000000232310332
Vilja PietiäinenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Cecilia M Lindgren1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Kari Stefansson1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Aarno Palotie1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [4] Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA. [5] Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Mark I McCarthy1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. [3] Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
Andrew P Morris1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Estonian Genome Center, University of Tartu, Tartu, Estonia. [3] Department of Biostatistics, University of Liverpool, Liverpool, UK.
Inga ProkopenkoDepartment of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
Samuli Ripatti1] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [2] Department of Public Health, University of Helsinki, Helsinki, Finland. [3] Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
ENGAGE Consortium

Funding

British Heart FoundationMedical Research Council G0902313Wellcome Trust 064890Wellcome Trust 069224Wellcome Trust 076113Wellcome Trust 098017Wellcome Trust WT090532
6 · The paper itself

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.

Indexed as

DyslipidemiasGene FrequencyGenetic LociGenome-Wide Association StudyHumansLinkage DisequilibriumLipid MetabolismMutation, MissensePolymorphism, Single NucleotideSequence Analysis, DNA

Identifiers

PMID25961943
PMCPMC4757735

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