Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorRASOOLY, Danielle
dc.contributor.authorPELOSO, Gina M.
dc.contributor.authorPEREIRA, Alexandre C.
dc.contributor.authorDASHTI, Hesam
dc.contributor.authorGIAMBARTOLOMEI, Claudia
dc.contributor.authorWHEELER, Eleanor
dc.contributor.authorAUNG, Nay
dc.contributor.authorFEROLITO, Brian R.
dc.contributor.authorPIETZNER, Maik
dc.contributor.authorFARBER-EGER, Eric H.
dc.contributor.authorWELLS, Quinn Stanton
dc.contributor.authorKOSIK, Nicole M.
dc.contributor.authorGAZIANO, Liam
dc.contributor.authorPOSNER, Daniel C.
dc.contributor.authorBENTO, A. Patricia
dc.contributor.authorHUI, Qin
dc.contributor.authorLIU, Chang
dc.contributor.authorARAGAM, Krishna
dc.contributor.authorWANG, Zeyuan
dc.contributor.authorCHAREST, Brian
dc.contributor.authorHUFFMAN, Jennifer E.
dc.contributor.authorWILSON, Peter W. F.
dc.contributor.authorPHILLIPS, Lawrence S.
dc.contributor.authorWHITTAKER, John
dc.contributor.authorMUNROE, Patricia B.
dc.contributor.authorPETERSEN, Steffen E.
dc.contributor.authorCHO, Kelly
dc.contributor.authorLEACH, Andrew R.
dc.contributor.authorMAGARINOS, Maria Paula
dc.contributor.authorGAZIANO, John Michael
dc.contributor.authorLANGENBERG, Claudia
dc.contributor.authorSUN, Yan V.
dc.contributor.authorJOSEPH, Jacob
dc.contributor.authorCASAS, Juan P.
dc.contributor.groupauthorVA Million Vet Program
dc.date.accessioned2023-10-30T15:21:59Z
dc.date.available2023-10-30T15:21:59Z
dc.date.issued2023
dc.description.abstractWe conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure. Here, the authors perform a large-scale meta-analysis of genome-wide association studies and cis-MR proteomics to identify protein biomarkers and drug targets for heart failure.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipDepartment of Veterans Affairs Office of Research and Development, Million Veteran Program [I01 CX001737, I01-BX004821, I01-CX001025]
dc.description.sponsorshipNational Health Service (NHS) Health Research Authority Research Ethics Committee [04/Q0108/19, 10.22025/2017.10.101.00001]
dc.description.sponsorshipMedical Research Council [MC_UU_12015/1, MC_PC_13046]
dc.description.sponsorshipUniversity of Cambridge
dc.description.sponsorshipNational Institute for Health and Care Research Barts Biomedical Research Centre [NIHR203330]
dc.description.sponsorshipBarts Health NHS Trust
dc.description.sponsorshipQueen Mary University of London, St George's University Hospitals NHS Foundation Trust
dc.description.sponsorshipSt George's University of London
dc.description.sponsorshipNIHR Integrated Academic Training program
dc.description.sponsorshipEuropean Union [754490MINDED project.L.S.P]
dc.description.sponsorshipVA awards CSP [I01 CX001737, I01 CX001899, I01 BX005831]
dc.description.sponsorshipNIH [R01 DK127083, R21 AI156161, UL1 TR002378, U18DP006711]
dc.description.sponsorshipCystic Fibrosis Foundation [PHILLI12A0]
dc.description.sponsorshipVeterans Health Administration (VA)
dc.description.sponsorshipNovartis Institute for Biomedical Research
dc.identifier.citationNATURE COMMUNICATIONS, v.14, n.1, 2023
dc.identifier.doi10.1038/s41467-023-39253-3
dc.identifier.eissn2041-1723
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/56418
dc.language.isoeng
dc.publisherNATURE PORTFOLIOeng
dc.relation.ispartofNature Communications
dc.rightsopenAccesseng
dc.rights.holderCopyright NATURE PORTFOLIOeng
dc.subject.othergenetic architectureeng
dc.subject.otherproteineng
dc.subject.othervolanesorseneng
dc.subject.wosMultidisciplinary Scienceseng
dc.titleGenome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failureeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryItália
hcfmusp.affiliation.countryInglaterra
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisoit
hcfmusp.affiliation.countryisogb
hcfmusp.author.externalRASOOLY, Danielle:Harvard Med Sch, Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02130 USA; VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.author.externalPELOSO, Gina M.:VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA; Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave Crosstown Ctr, Boston, MA 02118 USA
hcfmusp.author.externalDASHTI, Hesam:Harvard Med Sch, Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02130 USA; Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA
hcfmusp.author.externalGIAMBARTOLOMEI, Claudia:Human Technopole, Hlth Data Sci Ctr, Vle Rita Levi Montalcini 1, I-20157 Milan, Italy; Ist Italiano Tecnol, Cent RNA Lab, Noncoding RNAs & RNA based Therapeut, Via Morego 30, I-16163 Genoa, Italy
hcfmusp.author.externalWHEELER, Eleanor:Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, IMS, Box 285, Cambridge CB2 0QQ, England
hcfmusp.author.externalAUNG, Nay:Queen Mary Univ London, WilliamHarvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England; Barts Hlth NHS Trust, St Bartholomews Hosp, Barts Heart Ctr, London, England
hcfmusp.author.externalFEROLITO, Brian R.:VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.author.externalPIETZNER, Maik:Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, IMS, Box 285, Cambridge CB2 0QQ, England; Charite Univ Med Berlin, Berlin Inst Hlth BIH, Computat Med, Kapelle Ufer 2, D-10117 Berlin, Germany; Queen Mary Univ London, Precis Healthcare Univ Res Inst, London, England
hcfmusp.author.externalFARBER-EGER, Eric H.:Vanderbilt Univ, Vanderbilt Inst Clin & Translat Res, Med Ctr, Nashville, TN USA
hcfmusp.author.externalWELLS, Quinn Stanton:Vanderbilt Univ, Med Ctr, Dept Med Cardiol, Nashville, TN USA; Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA; Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN USA
hcfmusp.author.externalKOSIK, Nicole M.:VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.author.externalGAZIANO, Liam:VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA; Univ Cambridge, BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England
hcfmusp.author.externalPOSNER, Daniel C.:VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.author.externalBENTO, A. Patricia:Wellcome Genome Campus, European Bioinformat Inst, Dept Chem Biol, European Mol Biol Lab, Hinxton CB10 1SD, England
hcfmusp.author.externalHUI, Qin:Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA; Atlanta VA Hlth Care Syst, 1670 Clairmont Rd, Decatur, GA 30033 USA
hcfmusp.author.externalLIU, Chang:Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA
hcfmusp.author.externalARAGAM, Krishna:VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA; Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA; Massachusetts Gen Hosp, Boston, MA 02114 USA
hcfmusp.author.externalWANG, Zeyuan:Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA
hcfmusp.author.externalCHAREST, Brian:VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.author.externalHUFFMAN, Jennifer E.:VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.author.externalWILSON, Peter W. F.:Atlanta VA Hlth Care Syst, 1670 Clairmont Rd, Decatur, GA 30033 USA; Emory Univ, Dept Med, Div Cardiol, Sch Med, 1639 Pierce Dr NE, Atlanta, GA 30322 USA
hcfmusp.author.externalPHILLIPS, Lawrence S.:Atlanta VA Hlth Care Syst, 1670 Clairmont Rd, Decatur, GA 30033 USA; Emory Univ, Div Endocrinol, 101 Woodruff Circle,WMRB 1027, Atlanta, GA 30322 USA
hcfmusp.author.externalWHITTAKER, John:Univ Cambridge, MRC Biostat Unit, Cambridge CB2 0SR, England
hcfmusp.author.externalMUNROE, Patricia B.:Queen Mary Univ London, William Harvey Res Inst, Barts & London Fac Med & Dent, Charterhouse Sq, London EC1M 6BQ, England; Queen Mary Univ London, Natl Inst Hlth Res, Barts Biomed Res Ctr, London, England
hcfmusp.author.externalPETERSEN, Steffen E.:Barts Hlth NHS Trust, St Bartholomews Hosp, Barts Heart Ctr, London, England; Queen Mary Univ London, William Harvey Res Inst, NIHR Barts Biomed Res Ctr, Charterhouse Sq, London EC1M 68Q, England
hcfmusp.author.externalCHO, Kelly:Harvard Med Sch, Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02130 USA; VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.author.externalLEACH, Andrew R.:Wellcome Genome Campus, European Bioinformat Inst, Dept Chem Biol, European Mol Biol Lab, Hinxton CB10 1SD, England
hcfmusp.author.externalMAGARINOS, Maria Paula:Wellcome Genome Campus, European Bioinformat Inst, Dept Chem Biol, European Mol Biol Lab, Hinxton CB10 1SD, England
hcfmusp.author.externalGAZIANO, John Michael:Harvard Med Sch, Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02130 USA; VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.author.externalLANGENBERG, Claudia:Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, IMS, Box 285, Cambridge CB2 0QQ, England; Charite Univ Med Berlin, Berlin Inst Hlth BIH, Computat Med, Kapelle Ufer 2, D-10117 Berlin, Germany; Queen Mary Univ London, Precis Healthcare Univ Res Inst, London, England
hcfmusp.author.externalSUN, Yan V.:Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA; Atlanta VA Hlth Care Syst, 1670 Clairmont Rd, Decatur, GA 30033 USA; Emory Univ, Dept Biomed Informat, Sch Med, 1639 Pierce Dr NE, Atlanta, GA 30332 USA
hcfmusp.author.externalJOSEPH, Jacob:VA Providence Healthcare Syst, Cardiol Sect, 830 Chalkstone Ave, Providence, RI 02908 USA; Brown Univ, Dept Med, Warren Alpert Med Sch, 222 Richmond St, Providence, RI 02903 USA
hcfmusp.author.externalCASAS, Juan P.:Harvard Med Sch, Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02130 USA; VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, 150 S Huntington Ave, Boston, MA 02130 USA
hcfmusp.citation.scopus5
hcfmusp.contributor.author-fmusphcALEXANDRE DA COSTA PEREIRA
hcfmusp.description.issue1
hcfmusp.description.volume14
hcfmusp.origemWOS
hcfmusp.origem.pubmed37429843
hcfmusp.origem.scopus2-s2.0-85164294770
hcfmusp.origem.wosWOS:001027089000009
hcfmusp.publisher.cityBERLINeng
hcfmusp.publisher.countryGERMANYeng
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