Nature Communications (Apr 2025)
Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits
- 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
Affiliations
- Lauren E. Petty
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Hung-Hsin Chen
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Elizabeth G. Frankel
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Wanying Zhu
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Carolina G. Downie
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Mariaelisa Graff
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Phillip Lin
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Priya Sharma
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Xinruo Zhang
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Alyssa C. Scartozzi
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Rashedeh Roshani
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Joshua M. Landman
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Michael Boehnke
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan
- Donald W. Bowden
- Center for Precision Medicine, Wake Forest School of Medicine
- John C. Chambers
- Department of Epidemiology and Biostatistics, Imperial College London
- Anubha Mahajan
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford
- Mark I. McCarthy
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford
- Maggie C. Y. Ng
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Xueling Sim
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
- Cassandra N. Spracklen
- Department of Genetics, University of North Carolina at Chapel Hill
- Weihua Zhang
- Department of Epidemiology and Biostatistics, Imperial College London
- Michael Preuss
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Erwin P. Bottinger
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Girish N. Nadkarni
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Ruth J. F. Loos
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Yii-Der Ida Chen
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Jingyi Tan
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Eli Ipp
- Division of Endocrinology & Metabolism, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
- Pauline Genter
- Division of Endocrinology & Metabolism, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
- Leslie S. Emery
- Department of Biostatistics, University of Washington
- Tin Louie
- Department of Biostatistics, University of Washington
- Tamar Sofer
- Departments of Medicine and Biostatistics, Harvard University
- Adrienne M. Stilp
- Department of Biostatistics, University of Washington
- Kent D. Taylor
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Anny H. Xiang
- Department of Research & Evaluation, Division of Biostatistics Research, Kaiser Permanente of Southern California
- Thomas A. Buchanan
- Department of Medicine, Division of Endocrine, Keck School of Medicine of USC
- Kathryn Roll
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Chuan Gao
- Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-
- Nicholette D. Palmer
- Department of Biochemistry, Wake Forest School of Medicine
- Jill M. Norris
- Department of Epidemiology, University of Colorado Denver
- Lynne E. Wagenknecht
- Division of Public Health Sciences, Wake Forest School of Medicine
- Darryl Nousome
- Department of Preventative Medicine, Keck School of Medicine of the University of Southern California
- Rohit Varma
- Southern California Eye Institute, CHA Hollywood Presbyterian Medical Center
- Roberta McKean-Cowdin
- Department of Preventative Medicine, Keck School of Medicine of the University of Southern California
- Xiuqing Guo
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Yang Hai
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Willa Hsueh
- Department of Internal Medicine, Diabetes and Metabolism Research Center, Ohio State University Wexner Medical Center
- Kevin Sandow
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Esteban J. Parra
- Department of Anthropology, University of Toronto at Mississauga
- Miguel Cruz
- Unidad de Investigación Médica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSS
- Adan Valladares-Salgado
- Unidad de Investigación Médica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSS
- Niels Wacher-Rodarte
- Unidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSS
- Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Mark O. Goodarzi
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center
- Stephen S. Rich
- Center for Public Health Genomics, University of Virginia
- Alain Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine
- Leslie J. Raffel
- Department of Pediatrics, Division of Medical Genetics, UCI Irvine School of Medicine
- Jerry L. Nadler
- Department of Medicine and Pharmacology, New York Medical College
- Fouad R. Kandeel
- Departments of Clinical Diabetes, Endocrinology & Metabolism and Translational Research and Cellular Therapeutics, City of Hope
- Ravindranath Duggirala
- Human Genetics and STDOI, University of Texas Rio Grande Valley
- John Blangero
- Human Genetics and STDOI, University of Texas Rio Grande Valley
- Donna M. Lehman
- Department of Medicine, University of Texas Health Science Center at San Antonio
- Ralph A. DeFronzo
- Department of Medicine, University of Texas Health Science Center at San Antonio
- Farook Thameem
- Department of Biochemistry, Faculty of Medicine, Health Science Center, Kuwait University
- Yujie Wang
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Sheila Gahagan
- Division of Academic General Pediatrics, Child Development and Community Health, University of California at San Diego
- Estela Blanco
- College y Escuela de Salud Pública, Pontificia Universidad Católica de Chile
- Raquel Burrows
- Department of Public Health Nutrition, Institute of Nutrition and Food Technology, University of Chile
- Alicia Huerta-Chagoya
- Consejo Nacional de Ciencia y Tecnología (CONACYT), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
- Jose C. Florez
- Department of Medicine, Harvard Medical School
- Teresa Tusie-Luna
- Unidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
- Clicerio González-Villalpando
- Centro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Pública
- Lorena Orozco
- Instituto Nacional de Medicina Genómica
- Christopher A. Haiman
- Department of Population and Public Health Sciences, Keck School of Medicine of USC
- Craig L. Hanis
- Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston
- Rebecca Rohde
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Eric A. Whitsel
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Alexander P. Reiner
- Department of Epidemiology, University of Washington
- Charles Kooperberg
- Fred Hutchinson Cancer Research Center
- Yun Li
- Department of Genetics, University of North Carolina at Chapel Hill
- Qing Duan
- Department of Genetics, University of North Carolina at Chapel Hill
- Miryoung Lee
- Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional Campus
- Paulina Correa-Burrows
- Department of Public Health Nutrition, Institute of Nutrition and Food Technology, University of Chile
- Susan K. Fried
- Diabetes, Obesity Metabolism Institute, Icahn School of Medicine at Mount Sinai
- Kari E. North
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Joseph B. McCormick
- Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional Campus
- Susan P. Fisher-Hoch
- Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional Campus
- Eric R. Gamazon
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- Andrew P. Morris
- Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, University of Manchester
- Josep M. Mercader
- Department of Medicine, Harvard Medical School
- Heather M. Highland
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
- Jennifer E. Below
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center
- On behalf of the DIAMANTE Hispanic/Latino Consortium
- Global Hispanic Lipids Consortium
- DOI
- https://doi.org/10.1038/s41467-025-58574-z
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 13
Abstract
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.
