ArticleHuman molecular genetics2016
Analysis with the exome array identifies multiple new independent variants in lipid loci.
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Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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12citing papers in PubMed, 1 pooled it
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits.Nature communications · 2022Pooled it
- Update of a Genetic Risk Score Predictive of the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation in the FAS Study.Nutrients · 2023Article
- Identification of genetic loci simultaneously associated with multiple cardiometabolic traits.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2022Article
- Sclerostin Downregulation Globally by Naturally Occurring Genetic Variants, or Locally in Atherosclerotic Plaques, Does Not Associate With Cardiovascular Events in Humans.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels.Circulation. Genomic and precision medicine · 2020Article
- Article
- Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels.PloS one · 2019Article
- Phenotype-Specific Enrichment of Mendelian Disorder Genes near GWAS Regions across 62 Complex Traits.American journal of human genetics · 2018Article
- Cohort Profile: Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS).International journal of epidemiology · 2018Article
- A large electronic-health-record-based genome-wide study of serum lipids.Nature genetics · 2018Article
- HDL-cholesterol concentration in pregnant Chinese Han women of late second trimester associated with genetic variants inOncotarget · 2017Article
- The impact of rare and low-frequency genetic variants in common disease.Genome biology · 2017Review
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Authors and funding
62 authors.
Stavroula KanoniWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Nicholas G D MascaDepartment of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK.
Kathleen E StirrupsWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Tibor V VargaThe Broad Institute of MIT and Harvard, Boston, MA 02142, USA.
Helen R WarrenClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Robert A ScottMedical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
Lorraine SouthamWellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Weihua ZhangDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.
Hanieh YaghootkarGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Martina Müller-NurasyidDepartment of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
Alexessander Couto AlvesDepartment of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Rona J StrawbridgeAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Lazaros LataniotisWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Nikman An HashimSection of Investigative Medicine, Imperial College London, London, UK.
Céline BesseCEA, Institut de Génomique, Centre National de Génotypage, Evry, France.
Anne BolandCEA, Institut de Génomique, Centre National de Génotypage, Evry, France.
Peter S BraundDepartment of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK.
John M ConnellMedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Anna DominiczakDivision of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Western Infirmary, Glasgow, UK.
Aliki-Eleni FarmakiDepartment of Nutrition and Dietetics, School of Health Science and Education, Harokopio University Athens, Athens, Greece.
Stephen FranksDepartment of Surgery and Cancer, Imperial College London, Institute of Reproductive and Developmental Biology, London, UK.
Harald GrallertResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Jan-Håkan JanssonDepartment of Public Health and Clinical Medicine, Skellefteå Research Unit, Umeå University, Umeå, Sweden.
Maria KaraleftheriEchinos Medical Centre, Echinos, Greece.
Sirkka Keinänen-KiukaanniemiInstitute of Health Sciences, University of Oulu, Oulu, Finland.
Angela MatchanWellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Dorota PaskoGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Annette PetersDZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
Neil PoulterInternational Centre for Circulatory Health, Imperial College London, London, UK.
Nigel W RaynerWellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Frida RenströmDepartment of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
Olov RolandssonDepartment of Public Health & Clinical Medicine, Section for Family Medicine, Umeå University, Umeå, Sweden.
Maria Sabater-LlealAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Bengt SennbladAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Peter SeverInternational Centre for Circulatory Health, Imperial College London, London, UK.
Denis ShieldsComplex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin, Ireland.
Angela SilveiraAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Alice V StantonMolecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Stephens Green, Dublin, Ireland.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Maciej TomaszewskiDepartment of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK.
Emmanouil TsafantakisAnogia Medical Centre, Anogia, Greece.
Melanie WaldenbergerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Alexandra I F BlakemoreSection of Investigative Medicine, Imperial College London, London, UK.
George DedoussisDepartment of Nutrition and Dietetics, School of Health Science and Education, Harokopio University Athens, Athens, Greece.
Stefan A EscherDepartment of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
Jaspal S KoonerEaling Hospital NHS Trust, Middlesex, UK.
Mark I McCarthyWellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
Colin N A PalmerMedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Wellcome Trust Case Control Consortium
Anders HamstenAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Mark J CaulfieldWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Timothy M FraylingGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Martin D TobinDepartment of Health Sciences, University of Leicester, Leicester, UK.
Marjo-Riitta JarvelinDepartment of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Eleftheria ZegginiWellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Christian GiegerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
John C ChambersDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.
Nick J WarehamClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Patricia B MunroeWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Paul W FranksDepartment of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK p.deloukas@qmul.ac.uk.
Panos DeloukasWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK p.deloukas@qmul.ac.uk.
Funding
Genetics of cardiovascular risk factors in large founder population birth controlR01HL087679 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HIRSCHHORN, JOEL N · 2007 to 2009
$4.0MGenetic Influences on ADHD in a Finnish Birth CohortR01MH063706 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMALLEY, SUSAN L · 2001 to 2005
$3.3MWhole Genome Assoc. Analysis Strategies for Multi. PhenotypesRL1MH083268 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B. · 2007 to 2011
$2.1MBritish Heart Foundation RG/14/5/30893Medical Research Council G0401527Medical Research Council G0600237Medical Research Council G0601261Medical Research Council G0601966Medical Research Council G0700931Medical Research Council G0802782Medical Research Council G1000143Medical Research Council MR/K006584/1NHLBI NIH HHS R01 HL087679NIMH NIH HHS R01 MH063706NIMH NIH HHS RL1 MH083268Wellcome Trust
Abstract
It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
Indexed as
AdolescentAdultAgedChildCholesterol, HDLCholesterol, LDLExomeGene FrequencyGenome-Wide Association StudyHumansLipid MetabolismLipidsMiddle AgedPolymorphism, Single NucleotideTriglyceridesWhite PeopleCholesterol, HDLCholesterol, LDLLipidsTriglycerides
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.