IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58574-z.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58574-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58574-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Michael G. Levin & Noah L. Tsao & Pankhuri Singhal & Chang Liu & Ha My T. Vy & Ishan Paranjpe & Joshua D. Backman & Tiffany R. Bellomo & William P. Bone & Kiran J. Biddinger & Qin Hui & Ozan Dikilitas, 2022. "Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Jingning Zhang & Jianan Zhan & Jin Jin & Cheng Ma & Ruzhang Zhao & Jared O’Connell & Yunxuan Jiang & Bertram L. Koelsch & Haoyu Zhang & Nilanjan Chatterjee, 2024. "An ensemble penalized regression method for multi-ancestry polygenic risk prediction," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Leqi Xu & Geyu Zhou & Wei Jiang & Haoyu Zhang & Yikai Dong & Leying Guan & Hongyu Zhao, 2025. "JointPRS: A data-adaptive framework for multi-population genetic risk prediction incorporating genetic correlation," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    4. Benjamin M. Jacobs & Daniel Stow & Sam Hodgson & Julia Zöllner & Miriam Samuel & Stavroula Kanoni & Saeed Bidi & Klaudia Walter & Claudia Langenberg & Ruth Dobson & Sarah Finer & Caroline Morton & Mon, 2024. "Genetic architecture of routinely acquired blood tests in a British South Asian cohort," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. Ananyo Choudhury & Jean-Tristan Brandenburg & Tinashe Chikowore & Dhriti Sengupta & Palwende Romuald Boua & Nigel J. Crowther & Godfred Agongo & Gershim Asiki & F. Xavier Gómez-Olivé & Isaac Kisiangan, 2022. "Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Marta Alcalde-Herraiz & JunQing Xie & Danielle Newby & Clara Prats & Dipender Gill & María Gordillo-Marañón & Daniel Prieto-Alhambra & Martí Català & Albert Prats-Uribe, 2024. "Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Katrina G. Claw & Casey R. Dorr & Erica L. Woodahl, 2024. "Implementing community-engaged pharmacogenomics in Indigenous communities," Nature Communications, Nature, vol. 15(1), pages 1-5, December.
    9. Marie C. Sadler & Alexander Apostolov & Caterina Cevallos & Chiara Auwerx & Diogo M. Ribeiro & Russ B. Altman & Zoltán Kutalik, 2025. "Leveraging large-scale biobank EHRs to enhance pharmacogenetics of cardiometabolic disease medications," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    10. Shaan Khurshid & Julieta Lazarte & James P. Pirruccello & Lu-Chen Weng & Seung Hoan Choi & Amelia W. Hall & Xin Wang & Samuel F. Friedman & Victor Nauffal & Kiran J. Biddinger & Krishna G. Aragam & Pu, 2023. "Clinical and genetic associations of deep learning-derived cardiac magnetic resonance-based left ventricular mass," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    11. Nicole Deflaux & Margaret Sunitha Selvaraj & Henry Robert Condon & Kelsey Mayo & Sara Haidermota & Melissa A. Basford & Chris Lunt & Anthony A. Philippakis & Dan M. Roden & Joshua C. Denny & Anjene Mu, 2023. "Demonstrating paths for unlocking the value of cloud genomics through cross cohort analysis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    12. Eugene Lin & Yu-Ting Yan & Mu-Hong Chen & Albert C. Yang & Po-Hsiu Kuo & Shih-Jen Tsai, 2025. "Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    13. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Angela Wei & Richard Border & Boyang Fu & Sinéad Cullina & Nadav Brandes & Seon-Kyeong Jang & Sriram Sankararaman & Eimear E. Kenny & Miriam S. Udler & Vasilis Ntranos & Noah Zaitlen & Valerie A. Arbo, 2025. "Investigating the sources of variable impact of pathogenic variants in monogenic metabolic conditions," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    15. Diana Dunca & Sandesh Chopade & María Gordillo-Marañón & Aroon D. Hingorani & Karoline Kuchenbaecker & Chris Finan & Amand F. Schmidt, 2024. "Comparing the effects of CETP in East Asian and European ancestries: a Mendelian randomization study," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    16. Dmitrii Usoltsev & Nikita Kolosov & Oxana Rotar & Alexander Loboda & Maria Boyarinova & Ekaterina Moguchaya & Ekaterina Kolesova & Anastasia Erina & Kristina Tolkunova & Valeriia Rezapova & Ivan Molot, 2024. "Complex trait susceptibilities and population diversity in a sample of 4,145 Russians," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    17. Javier G. Serrano & Alejandra C. Ordóñez & Jonathan Santana & Elías Sánchez-Cañadillas & Matilde Arnay & Amelia Rodríguez-Rodríguez & Jacob Morales & Javier Velasco-Vázquez & Verónica Alberto-Barroso , 2023. "The genomic history of the indigenous people of the Canary Islands," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    18. Kimon Divaris & Gary D. Slade & Andrea G. Ferreira Zandona & John S. Preisser & Jeannie Ginnis & Miguel A. Simancas-Pallares & Cary S. Agler & Poojan Shrestha & Deepti S. Karhade & Apoena de Aguiar Ri, 2020. "Cohort Profile: ZOE 2.0—A Community-Based Genetic Epidemiologic Study of Early Childhood Oral Health," IJERPH, MDPI, vol. 17(21), pages 1-16, November.
    19. Xiaofeng Zhu & Yihe Yang & Noah Lorincz-Comi & Gen Li & Amy R. Bentley & Paul S. de Vries & Michael Brown & Alanna C. Morrison & Charles N. Rotimi & W. James Gauderman & Dabeeru C. Rao & Hugues Aschar, 2024. "An approach to identify gene-environment interactions and reveal new biological insight in complex traits," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    20. Injeong Shim & Hiroyuki Kuwahara & NingNing Chen & Mais O. Hashem & Lama AlAbdi & Mohamed Abouelhoda & Hong-Hee Won & Pradeep Natarajan & Patrick T. Ellinor & Amit V. Khera & Xin Gao & Fowzan S. Alkur, 2023. "Clinical utility of polygenic scores for cardiometabolic disease in Arabs," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58574-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.