Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits
Abstract Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci...
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2025-04-01
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| author | Lauren E. Petty Hung-Hsin Chen Elizabeth G. Frankel Wanying Zhu Carolina G. Downie Mariaelisa Graff Phillip Lin Priya Sharma Xinruo Zhang Alyssa C. Scartozzi Rashedeh Roshani Joshua M. Landman Michael Boehnke Donald W. Bowden John C. Chambers Anubha Mahajan Mark I. McCarthy Maggie C. Y. Ng Xueling Sim Cassandra N. Spracklen Weihua Zhang Michael Preuss Erwin P. Bottinger Girish N. Nadkarni Ruth J. F. Loos Yii-Der Ida Chen Jingyi Tan Eli Ipp Pauline Genter Leslie S. Emery Tin Louie Tamar Sofer Adrienne M. Stilp Kent D. Taylor Anny H. Xiang Thomas A. Buchanan Kathryn Roll Chuan Gao Nicholette D. Palmer Jill M. Norris Lynne E. Wagenknecht Darryl Nousome Rohit Varma Roberta McKean-Cowdin Xiuqing Guo Yang Hai Willa Hsueh Kevin Sandow Esteban J. Parra Miguel Cruz Adan Valladares-Salgado Niels Wacher-Rodarte Jerome I. Rotter Mark O. Goodarzi Stephen S. Rich Alain Bertoni Leslie J. Raffel Jerry L. Nadler Fouad R. Kandeel Ravindranath Duggirala John Blangero Donna M. Lehman Ralph A. DeFronzo Farook Thameem Yujie Wang Sheila Gahagan Estela Blanco Raquel Burrows Alicia Huerta-Chagoya Jose C. Florez Teresa Tusie-Luna Clicerio González-Villalpando Lorena Orozco Christopher A. Haiman Craig L. Hanis Rebecca Rohde Eric A. Whitsel Alexander P. Reiner Charles Kooperberg Yun Li Qing Duan Miryoung Lee Paulina Correa-Burrows Susan K. Fried Kari E. North Joseph B. McCormick Susan P. Fisher-Hoch Eric R. Gamazon Andrew P. Morris Josep M. Mercader Heather M. Highland Jennifer E. Below On behalf of the DIAMANTE Hispanic/Latino Consortium Global Hispanic Lipids Consortium |
| author_facet | Lauren E. Petty Hung-Hsin Chen Elizabeth G. Frankel Wanying Zhu Carolina G. Downie Mariaelisa Graff Phillip Lin Priya Sharma Xinruo Zhang Alyssa C. Scartozzi Rashedeh Roshani Joshua M. Landman Michael Boehnke Donald W. Bowden John C. Chambers Anubha Mahajan Mark I. McCarthy Maggie C. Y. Ng Xueling Sim Cassandra N. Spracklen Weihua Zhang Michael Preuss Erwin P. Bottinger Girish N. Nadkarni Ruth J. F. Loos Yii-Der Ida Chen Jingyi Tan Eli Ipp Pauline Genter Leslie S. Emery Tin Louie Tamar Sofer Adrienne M. Stilp Kent D. Taylor Anny H. Xiang Thomas A. Buchanan Kathryn Roll Chuan Gao Nicholette D. Palmer Jill M. Norris Lynne E. Wagenknecht Darryl Nousome Rohit Varma Roberta McKean-Cowdin Xiuqing Guo Yang Hai Willa Hsueh Kevin Sandow Esteban J. Parra Miguel Cruz Adan Valladares-Salgado Niels Wacher-Rodarte Jerome I. Rotter Mark O. Goodarzi Stephen S. Rich Alain Bertoni Leslie J. Raffel Jerry L. Nadler Fouad R. Kandeel Ravindranath Duggirala John Blangero Donna M. Lehman Ralph A. DeFronzo Farook Thameem Yujie Wang Sheila Gahagan Estela Blanco Raquel Burrows Alicia Huerta-Chagoya Jose C. Florez Teresa Tusie-Luna Clicerio González-Villalpando Lorena Orozco Christopher A. Haiman Craig L. Hanis Rebecca Rohde Eric A. Whitsel Alexander P. Reiner Charles Kooperberg Yun Li Qing Duan Miryoung Lee Paulina Correa-Burrows Susan K. Fried Kari E. North Joseph B. McCormick Susan P. Fisher-Hoch Eric R. Gamazon Andrew P. Morris Josep M. Mercader Heather M. Highland Jennifer E. Below On behalf of the DIAMANTE Hispanic/Latino Consortium Global Hispanic Lipids Consortium |
| author_sort | Lauren E. Petty |
| collection | DOAJ |
| description | Abstract Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes. |
| format | Article |
| id | doaj-art-8e6ba0aa1dca4bec8d333003f3cb43f8 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8e6ba0aa1dca4bec8d333003f3cb43f82025-08-20T03:06:57ZengNature PortfolioNature Communications2041-17232025-04-0116111310.1038/s41467-025-58574-zLarge-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traitsLauren E. Petty0Hung-Hsin Chen1Elizabeth G. Frankel2Wanying Zhu3Carolina G. Downie4Mariaelisa Graff5Phillip Lin6Priya Sharma7Xinruo Zhang8Alyssa C. Scartozzi9Rashedeh Roshani10Joshua M. Landman11Michael Boehnke12Donald W. Bowden13John C. Chambers14Anubha Mahajan15Mark I. McCarthy16Maggie C. Y. Ng17Xueling Sim18Cassandra N. Spracklen19Weihua Zhang20Michael Preuss21Erwin P. Bottinger22Girish N. Nadkarni23Ruth J. F. Loos24Yii-Der Ida Chen25Jingyi Tan26Eli Ipp27Pauline Genter28Leslie S. Emery29Tin Louie30Tamar Sofer31Adrienne M. Stilp32Kent D. Taylor33Anny H. Xiang34Thomas A. Buchanan35Kathryn Roll36Chuan Gao37Nicholette D. Palmer38Jill M. Norris39Lynne E. Wagenknecht40Darryl Nousome41Rohit Varma42Roberta McKean-Cowdin43Xiuqing Guo44Yang Hai45Willa Hsueh46Kevin Sandow47Esteban J. Parra48Miguel Cruz49Adan Valladares-Salgado50Niels Wacher-Rodarte51Jerome I. Rotter52Mark O. Goodarzi53Stephen S. Rich54Alain Bertoni55Leslie J. Raffel56Jerry L. Nadler57Fouad R. Kandeel58Ravindranath Duggirala59John Blangero60Donna M. Lehman61Ralph A. DeFronzo62Farook Thameem63Yujie Wang64Sheila Gahagan65Estela Blanco66Raquel Burrows67Alicia Huerta-Chagoya68Jose C. Florez69Teresa Tusie-Luna70Clicerio González-Villalpando71Lorena Orozco72Christopher A. Haiman73Craig L. Hanis74Rebecca Rohde75Eric A. Whitsel76Alexander P. Reiner77Charles Kooperberg78Yun Li79Qing Duan80Miryoung Lee81Paulina Correa-Burrows82Susan K. Fried83Kari E. North84Joseph B. McCormick85Susan P. Fisher-Hoch86Eric R. Gamazon87Andrew P. Morris88Josep M. Mercader89Heather M. Highland90Jennifer E. Below91On behalf of the DIAMANTE Hispanic/Latino ConsortiumGlobal Hispanic Lipids ConsortiumVanderbilt Genetics Institute, Vanderbilt University Medical CenterVanderbilt Genetics Institute, Vanderbilt University Medical CenterVanderbilt Genetics Institute, Vanderbilt University Medical CenterVanderbilt Genetics Institute, Vanderbilt University Medical CenterDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillVanderbilt Genetics Institute, Vanderbilt University Medical CenterDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillVanderbilt Genetics Institute, Vanderbilt University Medical CenterVanderbilt Genetics Institute, Vanderbilt University Medical CenterVanderbilt Genetics Institute, Vanderbilt University Medical CenterDepartment of Biostatistics and Center for Statistical Genetics, University of MichiganCenter for Precision Medicine, Wake Forest School of MedicineDepartment of Epidemiology and Biostatistics, Imperial College LondonOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of OxfordOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of OxfordVanderbilt Genetics Institute, Vanderbilt University Medical CenterSaw Swee Hock School of Public Health, National University of Singapore and National University Health SystemDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Epidemiology and Biostatistics, Imperial College LondonThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDivision of Endocrinology & Metabolism, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterDivision of Endocrinology & Metabolism, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterDepartment of Biostatistics, University of WashingtonDepartment of Biostatistics, University of WashingtonDepartments of Medicine and Biostatistics, Harvard UniversityDepartment of Biostatistics, University of WashingtonThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDepartment of Research & Evaluation, Division of Biostatistics Research, Kaiser Permanente of Southern CaliforniaDepartment of Medicine, Division of Endocrine, Keck School of Medicine of USCThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterMolecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Department of Biochemistry, Wake Forest School of MedicineDepartment of Epidemiology, University of Colorado DenverDivision of Public Health Sciences, Wake Forest School of MedicineDepartment of Preventative Medicine, Keck School of Medicine of the University of Southern CaliforniaSouthern California Eye Institute, CHA Hollywood Presbyterian Medical CenterDepartment of Preventative Medicine, Keck School of Medicine of the University of Southern CaliforniaThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDepartment of Internal Medicine, Diabetes and Metabolism Research Center, Ohio State University Wexner Medical CenterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDepartment of Anthropology, University of Toronto at MississaugaUnidad de Investigación Médica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSSUnidad de Investigación Médica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSSUnidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSSThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDepartment of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical CenterCenter for Public Health Genomics, University of VirginiaDepartment of Epidemiology and Prevention, Wake Forest School of MedicineDepartment of Pediatrics, Division of Medical Genetics, UCI Irvine School of MedicineDepartment of Medicine and Pharmacology, New York Medical CollegeDepartments of Clinical Diabetes, Endocrinology & Metabolism and Translational Research and Cellular Therapeutics, City of HopeHuman Genetics and STDOI, University of Texas Rio Grande ValleyHuman Genetics and STDOI, University of Texas Rio Grande ValleyDepartment of Medicine, University of Texas Health Science Center at San AntonioDepartment of Medicine, University of Texas Health Science Center at San AntonioDepartment of Biochemistry, Faculty of Medicine, Health Science Center, Kuwait UniversityDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillDivision of Academic General Pediatrics, Child Development and Community Health, University of California at San DiegoCollege y Escuela de Salud Pública, Pontificia Universidad Católica de ChileDepartment of Public Health Nutrition, Institute of Nutrition and Food Technology, University of ChileConsejo Nacional de Ciencia y Tecnología (CONACYT), Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránDepartment of Medicine, Harvard Medical SchoolUnidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránCentro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud PúblicaInstituto Nacional de Medicina GenómicaDepartment of Population and Public Health Sciences, Keck School of Medicine of USCHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at HoustonDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillDepartment of Epidemiology, University of WashingtonFred Hutchinson Cancer Research CenterDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional CampusDepartment of Public Health Nutrition, Institute of Nutrition and Food Technology, University of ChileDiabetes, Obesity Metabolism Institute, Icahn School of Medicine at Mount SinaiDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillDepartment of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional CampusDepartment of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional CampusVanderbilt Genetics Institute, Vanderbilt University Medical CenterCentre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, University of ManchesterDepartment of Medicine, Harvard Medical SchoolDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillVanderbilt Genetics Institute, Vanderbilt University Medical CenterAbstract Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes.https://doi.org/10.1038/s41467-025-58574-z |
| spellingShingle | Lauren E. Petty Hung-Hsin Chen Elizabeth G. Frankel Wanying Zhu Carolina G. Downie Mariaelisa Graff Phillip Lin Priya Sharma Xinruo Zhang Alyssa C. Scartozzi Rashedeh Roshani Joshua M. Landman Michael Boehnke Donald W. Bowden John C. Chambers Anubha Mahajan Mark I. McCarthy Maggie C. Y. Ng Xueling Sim Cassandra N. Spracklen Weihua Zhang Michael Preuss Erwin P. Bottinger Girish N. Nadkarni Ruth J. F. Loos Yii-Der Ida Chen Jingyi Tan Eli Ipp Pauline Genter Leslie S. Emery Tin Louie Tamar Sofer Adrienne M. Stilp Kent D. Taylor Anny H. Xiang Thomas A. Buchanan Kathryn Roll Chuan Gao Nicholette D. Palmer Jill M. Norris Lynne E. Wagenknecht Darryl Nousome Rohit Varma Roberta McKean-Cowdin Xiuqing Guo Yang Hai Willa Hsueh Kevin Sandow Esteban J. Parra Miguel Cruz Adan Valladares-Salgado Niels Wacher-Rodarte Jerome I. Rotter Mark O. Goodarzi Stephen S. Rich Alain Bertoni Leslie J. Raffel Jerry L. Nadler Fouad R. Kandeel Ravindranath Duggirala John Blangero Donna M. Lehman Ralph A. DeFronzo Farook Thameem Yujie Wang Sheila Gahagan Estela Blanco Raquel Burrows Alicia Huerta-Chagoya Jose C. Florez Teresa Tusie-Luna Clicerio González-Villalpando Lorena Orozco Christopher A. Haiman Craig L. Hanis Rebecca Rohde Eric A. Whitsel Alexander P. Reiner Charles Kooperberg Yun Li Qing Duan Miryoung Lee Paulina Correa-Burrows Susan K. Fried Kari E. North Joseph B. McCormick Susan P. Fisher-Hoch Eric R. Gamazon Andrew P. Morris Josep M. Mercader Heather M. Highland Jennifer E. Below On behalf of the DIAMANTE Hispanic/Latino Consortium Global Hispanic Lipids Consortium Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits Nature Communications |
| title | Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits |
| title_full | Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits |
| title_fullStr | Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits |
| title_full_unstemmed | Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits |
| title_short | Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits |
| title_sort | large scale multi omics analyses in hispanic latino populations identify genes for cardiometabolic traits |
| url | https://doi.org/10.1038/s41467-025-58574-z |
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