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Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits

Author

Listed:
  • Lauren E. Petty

    (Vanderbilt University Medical Center)

  • Hung-Hsin Chen

    (Vanderbilt University Medical Center
    Academia Sinica)

  • Elizabeth G. Frankel

    (Vanderbilt University Medical Center)

  • Wanying Zhu

    (Vanderbilt University Medical Center)

  • Carolina G. Downie

    (University of North Carolina at Chapel Hill)

  • Mariaelisa Graff

    (University of North Carolina at Chapel Hill)

  • Phillip Lin

    (Vanderbilt University Medical Center)

  • Priya Sharma

    (University of North Carolina at Chapel Hill)

  • Xinruo Zhang

    (University of North Carolina at Chapel Hill)

  • Alyssa C. Scartozzi

    (Vanderbilt University Medical Center)

  • Rashedeh Roshani

    (Vanderbilt University Medical Center)

  • Joshua M. Landman

    (Vanderbilt University Medical Center)

  • Michael Boehnke

    (University of Michigan)

  • Donald W. Bowden

    (Wake Forest School of Medicine
    Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • John C. Chambers

    (Imperial College London
    London North West Healthcare NHS Trust
    Nanyang Technological University
    Imperial College London)

  • Anubha Mahajan

    (University of Oxford
    University of Oxford)

  • Mark I. McCarthy

    (University of Oxford
    University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

  • Maggie C. Y. Ng

    (Vanderbilt University Medical Center
    Wake Forest School of Medicine
    Wake Forest School of Medicine
    Vanderbilt University Medical Center)

  • Xueling Sim

    (National University of Singapore and National University Health System)

  • Cassandra N. Spracklen

    (University of North Carolina at Chapel Hill
    University of Massachusetts-Amherst)

  • Weihua Zhang

    (Imperial College London
    London North West Healthcare NHS Trust)

  • Michael Preuss

    (Icahn School of Medicine at Mount Sinai)

  • Erwin P. Bottinger

    (Icahn School of Medicine at Mount Sinai)

  • Girish N. Nadkarni

    (Icahn School of Medicine at Mount Sinai
    Hasso-Plattner-Institut)

  • Ruth J. F. Loos

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Yii-Der Ida Chen

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center)

  • Jingyi Tan

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center)

  • Eli Ipp

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Pauline Genter

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • Leslie S. Emery

    (University of Washington)

  • Tin Louie

    (University of Washington)

  • Tamar Sofer

    (Harvard University
    Harvard Medical School
    Brigham and Women’s Hospital)

  • Adrienne M. Stilp

    (University of Washington)

  • Kent D. Taylor

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center)

  • Anny H. Xiang

    (Kaiser Permanente of Southern California)

  • Thomas A. Buchanan

    (Keck School of Medicine of USC)

  • Kathryn Roll

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center)

  • Chuan Gao

    (Winston-)

  • Nicholette D. Palmer

    (Wake Forest School of Medicine)

  • Jill M. Norris

    (University of Colorado Denver)

  • Lynne E. Wagenknecht

    (Wake Forest School of Medicine)

  • Darryl Nousome

    (Keck School of Medicine of the University of Southern California)

  • Rohit Varma

    (CHA Hollywood Presbyterian Medical Center)

  • Roberta McKean-Cowdin

    (Keck School of Medicine of the University of Southern California)

  • Xiuqing Guo

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center)

  • Yang Hai

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center)

  • Willa Hsueh

    (Ohio State University Wexner Medical Center)

  • Kevin Sandow

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center)

  • Esteban J. Parra

    (University of Toronto at Mississauga)

  • Miguel Cruz

    (IMSS)

  • Adan Valladares-Salgado

    (IMSS)

  • Niels Wacher-Rodarte

    (Centro Medico Nacional Siglo XXI, IMSS)

  • Jerome I. Rotter

    (The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center)

  • Mark O. Goodarzi

    (Cedars-Sinai Medical Center)

  • Stephen S. Rich

    (University of Virginia)

  • Alain Bertoni

    (Wake Forest School of Medicine)

  • Leslie J. Raffel

    (UCI Irvine School of Medicine)

  • Jerry L. Nadler

    (New York Medical College)

  • Fouad R. Kandeel

    (City of Hope)

  • Ravindranath Duggirala

    (University of Texas Rio Grande Valley)

  • John Blangero

    (University of Texas Rio Grande Valley)

  • Donna M. Lehman

    (University of Texas Health Science Center at San Antonio)

  • Ralph A. DeFronzo

    (University of Texas Health Science Center at San Antonio)

  • Farook Thameem

    (Kuwait University)

  • Yujie Wang

    (University of North Carolina at Chapel Hill)

  • Sheila Gahagan

    (University of California at San Diego)

  • Estela Blanco

    (Pontificia Universidad Católica de Chile)

  • Raquel Burrows

    (University of Chile)

  • Alicia Huerta-Chagoya

    (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Jose C. Florez

    (Harvard Medical School
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Teresa Tusie-Luna

    (Universidad Nacional Autónoma de México/Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán)

  • Clicerio González-Villalpando

    (Instituto Nacional de Salud Pública)

  • Lorena Orozco

    (Instituto Nacional de Medicina Genómica)

  • Christopher A. Haiman

    (Keck School of Medicine of USC)

  • Craig L. Hanis

    (The University of Texas Health Science Center at Houston)

  • Rebecca Rohde

    (University of North Carolina at Chapel Hill)

  • Eric A. Whitsel

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Alexander P. Reiner

    (University of Washington
    Fred Hutchinson Cancer Research Center)

  • Charles Kooperberg

    (Fred Hutchinson Cancer Research Center)

  • Yun Li

    (University of North Carolina at Chapel Hill)

  • Qing Duan

    (University of North Carolina at Chapel Hill)

  • Miryoung Lee

    (University of Texas Health Science Center at Houston, Brownsville Regional Campus)

  • Paulina Correa-Burrows

    (University of Chile)

  • Susan K. Fried

    (Icahn School of Medicine at Mount Sinai)

  • Kari E. North

    (University of North Carolina at Chapel Hill)

  • Joseph B. McCormick

    (University of Texas Health Science Center at Houston, Brownsville Regional Campus)

  • Susan P. Fisher-Hoch

    (University of Texas Health Science Center at Houston, Brownsville Regional Campus)

  • Eric R. Gamazon

    (Vanderbilt University Medical Center
    University of Cambridge)

  • Andrew P. Morris

    (University of Manchester)

  • Josep M. Mercader

    (Harvard Medical School
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Heather M. Highland

    (University of North Carolina at Chapel Hill)

  • Jennifer E. Below

    (Vanderbilt University Medical Center)

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.

Suggested Citation

  • 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 & Jos, 2025. "Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58574-z
    DOI: 10.1038/s41467-025-58574-z
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    References listed on IDEAS

    as
    1. Yao Hu & Mariaelisa Graff & Jeffrey Haessler & Steven Buyske & Stephanie A Bien & Ran Tao & Heather M Highland & Katherine K Nishimura & Niha Zubair & Yingchang Lu & Marie Verbanck & Austin T Hilliard, 2020. "Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study," PLOS Genetics, Public Library of Science, vol. 16(3), pages 1-19, March.
    2. Genevieve L. Wojcik & Mariaelisa Graff & Katherine K. Nishimura & Ran Tao & Jeffrey Haessler & Christopher R. Gignoux & Heather M. Highland & Yesha M. Patel & Elena P. Sorokin & Christy L. Avery & Gil, 2019. "Genetic analyses of diverse populations improves discovery for complex traits," Nature, Nature, vol. 570(7762), pages 514-518, June.
    3. Sarah E. Graham & Shoa L. Clarke & Kuan-Han H. Wu & Stavroula Kanoni & Greg J. M. Zajac & Shweta Ramdas & Ida Surakka & Ioanna Ntalla & Sailaja Vedantam & Thomas W. Winkler & Adam E. Locke & Eirini Ma, 2021. "The power of genetic diversity in genome-wide association studies of lipids," Nature, Nature, vol. 600(7890), pages 675-679, December.
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