ArticleScience (New York, N.Y.)2016
Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease.
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In one paragraph
Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 303 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
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303citing papers in PubMed, 4 pooled it
61.2field-weighted citation impact, top 1% of its field
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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.
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Who cites it
303 citing papers in PubMed, 4 syntheses or guidelines pooled it, 540 citations in OpenAlex.
- Effect of oat supplementation interventions on cardiovascular disease risk markers: a systematic review and meta-analysis of randomized controlled trials.European journal of nutrition · 2022Pooled it
- A dose-response meta-analysis to evaluate the relationship between high-density lipoprotein cholesterol and all-cause and cardiovascular disease mortality.Journal of endocrinological investigation · 2022Pooled it
- Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis.Nature communications · 2022Pooled it
- In-depth Mendelian randomization analysis of causal factors for coronary artery disease.Scientific reports · 2020Pooled it
- Effects of niacin and omega-3 fatty acids on HDL-apolipoprotein A-I exchange in subjects with metabolic syndrome.PloS one · 2024Trial
- Pharmacological Inhibition of CETP (Cholesteryl Ester Transfer Protein) Increases HDL (High-Density Lipoprotein) That Contains ApoC3 and Other HDL Subspecies Associated With Higher Risk of Coronary Heart Disease.Arteriosclerosis, thrombosis, and vascular biology · 2022Trial
- High-sensitivity CRP may be a marker of HDL dysfunction and remodeling in patients with acute coronary syndrome.Scientific reports · 2021Trial
- Anti-Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical Trial.Journal of the American Heart Association · 2020 · on this mapTrial
- Six years' experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias.BMC medical genomics · 2020Trial
- COPI Coatomer Regulates Several Steps of HDL Metabolism.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Reconceptualizing Dyslipidemia: Diversity of Lipid Imbalances and Their Clinical Implications; A Narrative Review.Health science reports · 2026Article
- High-density lipoprotein cholesterol: function, dysfunction, and clinical implications.American journal of preventive cardiology · 2026Article
- The association of childhood HDL cholesterol with atherosclerotic cardiovascular disease events in adults: findings from the International Childhood Cardiovascular Cohort Consortium.European journal of preventive cardiology · 2026Article
- Kernelized approach enables explainable gene prioritizations for complex traits.bioRxiv : the preprint server for biology · 2026Article
- Review
- Maternal circulating lipid metabolic heterogeneity in preeclampsia: machine learning identifies clinically distinct subtypes.BMC pregnancy and childbirth · 2026Article
- Long-term artificial sweetener exposure increases the risk of atherosclerosis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- From Adipose Tissue to Cardiac Repair: Extracellular Vesicles in Cardiovascular Regeneration.Journal of cellular and molecular medicine · 2026Review
- Impact of high-density lipoprotein cholesterol on cardiovascular diseases and all-cause mortality: a large-scale cohort study in Korea.Scientific reports · 2026Article
- The Association Between Cholesterol, High-Density Lipoprotein, and Glucose Index and Mortality in Young and Middle-Aged Adults With Diabetes or Prediabetes: NHANES Data (1999-2018).Cardiology research · 2026Article
243 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
52 authors at 20 institutions in 10 countries.
Paolo ZanoniDepartments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sumeet A KhetarpalDepartments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Daniel B LarachDepartments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
William F Hancock-CeruttiDepartments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. INSERM UMR 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitié, Paris, France.
John S MillarDepartments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Marina CuchelDepartments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Stephanie DerOhannessianDepartments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anatol KontushINSERM UMR 1166 ICAN, Université Pierre et Marie Curie Paris 6, Hôpital de la Pitié, Paris, France.
Praveen SurendranCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Danish SaleheenCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Centre for Non-Communicable Diseases, Karachi, Pakistan.
Stella TrompetDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands. Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, Netherlands. The Interuniversity Cardiology Institute of the Netherlands, Utrecht, Netherlands.
Anton De CraenDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.
Panos DeloukasWellcome Trust Sanger Institute, Genome Campus, Hinxton, UK.
Naveed SattarInstitute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Ian FordRobertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
Chris PackardGlasgow Clinical Research Facility, Western Infirmary, Glasgow, UK.
Abdullah al Shafi MajumderNational Institute of Cardiovascular Diseases, Sher-e-Bangla Nagar, Dhaka, Bangladesh.
Dewan S AlamInternational Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh.
Emanuele Di AngelantonioCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Goncalo AbecasisCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Rajiv ChowdhuryCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Jeanette ErdmannInstitute for Integrative and Experimental Genomics, University of Lübeck, Lübeck 23562, Germany.
Børge G NordestgaardDepartment of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Sune F NielsenDepartment of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Anne Tybjærg-HansenCopenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
Ruth Frikke SchmidtDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark.
Kari KuulasmaaDepartment of Health, National Institute for Health and Welfare, Helsinki, Finland.
Dajiang J LiuDepartment of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
Markus PerolaDepartment of Health, National Institute for Health and Welfare, Helsinki, Finland. Institute of Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
Stefan BlankenbergDepartment of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany. University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Veikko SalomaaDepartment of Health, National Institute for Health and Welfare, Helsinki, Finland.
Satu MännistöDepartment of Health, National Institute for Health and Welfare, Helsinki, Finland.
Philippe AmouyelDepartment of Epidemiology and Public Health, Institut Pasteur de Lille, Lille, France.
Dominique ArveilerDepartment of Epidemiology and Public Health, University of Strasbourg, Strasbourg, France.
Jean FerrieresDepartment of Epidemiology, Toulouse University-CHU Toulouse, Toulouse, France.
Martina Müller-NurasyidInstitute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany.
Marco FerrarioResearch Centre in Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
Frank KeeUKCRC Centre of Excellence for Public Health, Queens University, Belfast, Northern Ireland.
Cristen J WillerDepartment of Computational Medicine and Bioinformatics, Department of Human Genetics, and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Nilesh SamaniDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK. National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hotel, Leicester, UK.
Heribert SchunkertDeutsches Herzzentrum München, Technische Universität München, Munich, Germany.
Adam S ButterworthCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Joanna M M HowsonCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Gina M PelosoBroad Institute and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Nathan O StitzielDepartment of Medicine, Division of Cardiology, Department of Genetics, and the McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
John DaneshCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK.
Sekar KathiresanBroad Institute and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Daniel J RaderDepartments of Genetics and Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. rader@mail.med.upenn.edu.
CHD Exome+ Consortium
CARDIoGRAM Exome Consortium
Global Lipids Genetics Consortium
Translational Therapeutics (United States) · USUniversity of Cambridge · GBFinnish Institute for Health and Welfare · FIUniversität Hamburg · DEUniversity of Copenhagen · DKHelmholtz Zentrum München · DEInserm · FRLeiden University Medical Center · NLUniversité de Strasbourg · FRBroad Institute · USHerlev Hospital · DKInstitut Pasteur de Lille · FRUniversity of Michigan · USWellcome Sanger Institute · GBWestern Infirmary · GBBritish Heart Foundation · GBDeutsches Herzzentrum München · DEInstitute for Integrative and Experimental Genomics · DEInternational Centre for Diarrhoeal Disease Research · BDNational Institute of Cardiovascular Diseases · BD
Funding
iPS-derived hepatocytes for interrogation of lipid phenotypesU01HG006398 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI RADER, DANIEL JAMES · 2011 to 2015
$8.6MGenetic Architecture of Adiposity in Multiple Large CohortsR01DK089256 · NIDDK · WASHINGTON UNIVERSITY · PI BARANSKI, THOMAS JOHN, LIU, CHING-TI · 2010 to 2016
$4.6MGenetics of Elevated High Density Lipoprotein CholesterolR01HL089309 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI RADER, DANIEL JAMES · 2008 to 2012
$3.9MDiscovery and Validation of Novel Loci Associated with HDL FunctionR01HL111398 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DANESH, JOHN NAVID, RADER, DANIEL JAMES · 2012 to 2016
$3.3MProbing The Dark Matter of the Genome in the NHLBI Family Heart StudyR01HL117078 · NHLBI · WASHINGTON UNIVERSITY · PI PROVINCE, MICHAEL A. · 2013 to 2016
$3.0MGenome-wide Association Scan to Identify Risk Genes for Type 2 Diabetes in AsianR01DK082766 · NIDDK · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SANGHERA, DHARAMBIR K. · 2009 to 2011
$2.3MMethod to Enhance the Rare Variant Genetic Architecture Analysis in Meta-AnalysesR01HG008983 · NHGRI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LIU, DAJIANG · 2016 to 2019
$1.6MInstitutional Clinical and Translational Science AwardTL1RR024133 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2006 to 2011
$1.3MRare coding variation and risk for myocardial infarctionK08HL114642 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2012 to 2016
$703kMethods to Unveil the Genetic Architecture for Nicotine Dependence via NGS dataR21DA040177 · NIDA · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LIU, DAJIANG · 2015 to 2016
$447kBritish Heart Foundation PG/08/094/26019British Heart Foundation RG/08/014/24067British Heart Foundation RG/13/13/30194British Heart Foundation RG/14/5/30893Medical Research Council G0401527Medical Research Council G0800270Medical Research Council G0801566Medical Research Council MR/K013351/1Medical Research Council MR/L003120/1Medical Research Council MR/N003284/1NCRR NIH HHS TL1 RR024133NCRR NIH HHS TL1RR024133NHGRI NIH HHS R01 HG008983NHGRI NIH HHS U01 HG006398NHLBI NIH HHS K08 HL114642NHLBI NIH HHS R01 HL089309NHLBI NIH HHS R01 HL111398NHLBI NIH HHS R01 HL117078NIDA NIH HHS R21 DA040177NIDDK NIH HHS R01 DK082766NIDDK NIH HHS R01 DK089256
Abstract
Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).
Indexed as
AgedAmino Acid SubstitutionAnimalsCholesterol, HDLCoronary DiseaseDNA Mutational AnalysisFemaleGenetic VariationHeterozygoteHomozygoteHumansLeucineMaleMiceMiddle AgedProlineCholesterol, HDLLeucineProlineSCARB1 protein, humanScavenger Receptors, Class B
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