ArticleNature communications2020
Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 4 pooled it
19.4field-weighted citation impact, top 1% of its field
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Who cites it
44 citing papers in PubMed, 4 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Meta-analysis across six global biobanks identifies recessive coding associations with complex traits and diseases.American journal of human genetics · 2026Pooled it
- Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.Genome biology · 2022Pooled it
- Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT.Communications biology · 2022Pooled it
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- Risk of bias assessment for Mendelian randomisation studies: a guide.European journal of epidemiology · 2026Article
- Combining xQTL and genome-wide association studies from diverse populations improves druggable gene discovery.Nature communications · 2026Article
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- Lipoprotein lipase requires a flexible lid and stable C-terminal, both maintained by ApoC-II peptide binding.bioRxiv : the preprint server for biology · 2025Article
- A scalable framework for identifying allelic series from summary statistics.American journal of human genetics · 2025Article
- ZNF529 up-regulation speeds up progression and induces tyrosine kinase inhibitor resistance in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2025Article
- Spatiotemporal and demographic patterns of SARS-CoV-2 entry gene expression in a Lebanese cohort.Molecular biology reports · 2025Article
- Transgenic inducible MHC I overexpression in mouse alveolar type 2 cells.Transgenic research · 2025Article
- Identification of quantitative trait loci and candidate genes underlying kernel traits of wheat (Triticum aestivum L.) in response to drought stress.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2025Article
- Multi-cohort genome-wide association analyses reveal loci underlying circulating liver enzyme levels in African-ancestry populations.Research square · 2025Article
- Multitrait Genetic Analysis Identifies Novel Pleiotropic Loci for Depression and Schizophrenia in East Asians.Schizophrenia bulletin · 2025Article
- How does oxytocin modulate human behavior?Molecular psychiatry · 2025Review
- Cholesterol 7 alpha-hydroxylase (Biomolecules & biomedicine · 2025Article
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- Genetic analysis of cis-enhancers associated with bone mineral density and periodontitis in the gene SOST.PloS one · 2025Article
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Authors and funding
107 authors at 20 institutions in 6 countries.
Jonas B NielsenDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA. jonas.bille.nielsen@gmail.com.ORCID 0000-0002-6654-2852
Oren RomDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Ida SurakkaDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Sarah E GrahamDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-1271-2489
Wei ZhouProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0001-7719-0859
Tanmoy RoychowdhuryDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Lars G FritscheDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-2110-1690
Sarah A Gagliano TaliunDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0003-1306-1868
Carlo SidoreIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.ORCID 0000-0001-7504-7477
Yuhao LiuDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Maiken E GabrielsenK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Anne Heidi SkogholtK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Brooke WolfordDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-3153-1552
William OvertonDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Ying ZhaoDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Jin ChenDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
He ZhangDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-9198-6503
Whitney E HornsbyDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Akua AcheampongDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Austen GroomsDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Amanda SchaeferDepartment of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Gregory J M ZajacDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0001-6411-9666
Luis VillacortaDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-7824-7028
Jifeng ZhangDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA.
Ben BrumptonK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.ORCID 0000-0002-3058-1059
Mari LøsetK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.ORCID 0000-0003-3736-6551
Vivek RaiDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Pia R LundegaardLaboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-8284-1844
Morten S OlesenLaboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0001-9477-5322
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, CA, USA.ORCID 0000-0002-2756-4370
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.ORCID 0000-0001-8883-2511
Yii-Der ChenThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, CA, USA.
Seung H ChoiProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Steven A LubitzProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Patrick T EllinorProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-2067-0533
Kathleen C BarnesColorado Center for Personalized Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.ORCID 0000-0002-3030-4705
Michelle DayaColorado Center for Personalized Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.ORCID 0000-0002-9057-6593
Nicholas RafaelsColorado Center for Personalized Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.
Scott T WeissChanning Division of Network Medicine, Department of Medicine Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0001-7196-303X
Jessica Lasky-SuChanning Division of Network Medicine, Department of Medicine Brigham and Women's Hospital, Boston, MA, USA.
Russell P TracyDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.ORCID 0000-0002-0080-2420
Ramachandran S VasanDepartment of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA.ORCID 0000-0001-7357-5970
L Adrienne CupplesFramingham Heart Study, Framingham, MA, USA.ORCID 0000-0003-0273-7965
Rasika A MathiasGeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Lisa R YanekGeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-7117-1075
Lewis C BeckerGeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-9717-8459
Lawrence F BielakDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3443-8030
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3575-5468
Stella AslibekyanThe University of Alabama at Birmingham, Birmingham, AL, USA.
Bertha A HidalgoThe University of Alabama at Birmingham, Birmingham, AL, USA.
Donna K ArnettDeans Office, College of Public Health, University of Kentucky, Lexington, KY, USA.
Marguerite R IrvinThe University of Alabama at Birmingham, Birmingham, AL, USA.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
Solomon K MusaniJackson Heart Study, Jackson, MS, USA.
Adolfo CorreaJackson Heart Study, Jackson, MS, USA.ORCID 0000-0002-9501-600X
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0003-3872-7793
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, CA, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, CA, USA.ORCID 0000-0001-7191-1723
Barbara A KonkleBloodWorks Northwest, University of Washington, Seattle, WA, USA.
Jill M JohnsenBloodWorks Northwest, University of Washington, Seattle, WA, USA.
Allison E Ashley-KochDuke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0001-5409-9155
Marilyn J TelenDepartment of Medicine, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0003-3809-1780
Vivien A SheehanDepartment of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0003-2837-2255
John BlangeroDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.ORCID 0000-0001-6250-5723
Joanne E CurranDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Juan M PeraltaDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.ORCID 0000-0002-8811-5579
Courtney MontgomeryDepartment of Genes and Human Disease, Oklahoma Medical Research Foundation, Oklahoma, OK, USA.
Wayne H-H SheuDivision of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Ren-Hua ChungInstitute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
Karen SchwanderDivision of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
Seyed M NouraieUniversity of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Victor R GordeukUniversity of Illinois at Chicago, Chicago, IL, USA.
Yingze ZhangUniversity of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Alexander P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Rebecca D JacksonDivision of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, OH, USA.
Eugene R BleeckerDivision of Pharmacogenomics University of Arizona, Tucson, AR, USA.
Deborah A MeyersDivision of Pharmacogenomics University of Arizona, Tucson, AR, USA.
Xingnan LiDivision of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AR, USA.ORCID 0000-0002-1208-8658
Sayantan DasDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-6346-1590
Ketian YuDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0001-9994-3399
Jonathon LeFaiveDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0003-3668-6086
Albert SmithDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0003-1942-5845
Tom BlackwellDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Daniel TaliunDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Sebastian ZollnerDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Lukas ForerDivision of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AR, USA.
Sebastian SchoenherrInstitute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Christian FuchsbergerDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Anita PanditDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Matthew ZawistowskiDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0002-3005-083X
Sachin KheterpalDepartment of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
Chad M BrummettDepartment of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
Pradeep NatarajanProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0001-8402-7435
David SchlessingerLaboratory of Genetics, National Institute on Aging, US National Institutes of Health, Baltimore, MD, USA.
Seunggeun LeeDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0002-8097-3878
Hyun Min KangDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Francesco CuccaIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.ORCID 0000-0002-7414-1995
Oddgeir L HolmenK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Bjørn O ÅsvoldK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.ORCID 0000-0003-3837-2101
Michael BoehnkeDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0002-6442-7754
Sekar KathiresanHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-6724-032X
Goncalo R AbecasisDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0003-1509-1825
Y Eugene ChenDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA. echenum@umich.edu.ORCID 0000-0003-2357-7825
Cristen J WillerDepartment of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, MI, USA. cristen@umich.edu.ORCID 0000-0001-5645-4966
Kristian HveemK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway. kristian.hveem@ntnu.no.
University of Michigan · USNorwegian University of Science and Technology · NOBroad Institute · USThe Lundquist Institute · USUniversity of Arizona · USJackson Memorial Hospital · USJohns Hopkins University · USThe University of Texas Rio Grande Valley · USUniversity of Alabama at Birmingham · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Washington · USBoston University · USBrigham and Women's Hospital · USDuke Medical Center · USUniversity of Copenhagen · DKUniversity of Pittsburgh · USBaylor College of Medicine · USEurac Research · ITFred Hutch Cancer Center · USInnsbruck Medical University · AT
Funding
University of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4MIdentifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6MStudies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MUsing genetics to discover mechanisms of myocardial infarctionR01HL109946 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YUQING Eugene CHEN, Ida Liisa Surakka · 2011 to 2026
$8.9MGENETICS & EPIDEMIOLOGY OF AGAING - ASSOCIATED CONDITIONS IN THE SARDINIAN POPULN01AG12109 · NIA · CONSIGLIO NAZIONALE DELLE RICERCHE · PI UDA, MANUELA · 2007 to 2011
$7.8MThe Role of PPAR-gamma in Vascular Lesion FormationR01HL068878 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2002 to 2019
$7.6MUsing genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3MIdentifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7MStudies of Rare Genetic Variation in the Isolated Population of SardiniaU01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2017 to 2018
$6.3MUsing Genetics to Inform Mechanism of Cardiovascular DiseaseR35HL135824 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLER, CRISTEN J · 2017 to 2022
$5.4MMulti-omic studies of asthma severity in an African ancestry populationR01AI132476 · NIAID · UNIVERSITY OF COLORADO DENVER · PI BARNES, KATHLEEN C, MATHIAS, RASIKA ANN · 2018 to 2022
$3.5MNHGRI NIH HHS T32 HG000040NHLBI NIH HHS K08 HL140203NHLBI NIH HHS K99 HL150233NHLBI NIH HHS R01 HL068878NHLBI NIH HHS R01 HL109946NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL123333NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL130705NHLBI NIH HHS R01 HL137214NHLBI NIH HHS R01 HL138139NHLBI NIH HHS R01 HL139731NHLBI NIH HHS R35 HL135824NHLBI NIH HHS U01 HL117626NIAID NIH HHS R01 AI132476NIA NIH HHS N01AG12109NIDA NIH HHS HHSN271201100005CNIDDK NIH HHS R01 DK062370NIDDK NIH HHS U01 DK062370
Abstract
Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10
Indexed as
Genome, HumanMolecular Targeted TherapyBiological Specimen BanksCardiovascular DiseasesGene SilencingGene TargetingGenome-Wide Association StudyHumansLipidsLiverLoss of Function MutationPhenomicsReceptors, LDLUnited KingdomLDLR protein, humanLipidsReceptors, LDL
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