ArticleCommunications biology2025
Association of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program.
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Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1citing papers in PubMed
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Who cites it
1 citing paper in PubMed.
- Shared genetic and molecular architecture between insulin resistance and cognitive performance.medRxiv : the preprint server for health sciences · 2026Article
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Authors and funding
74 authors.
Chloé SarnowskiDepartment of Epidemiology, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA. Chloe.Sarnowski@uth.tmc.edu.ORCID http://orcid.org/0000-0002-6090-7099
Yixin ZhangDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Farah AmmousDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-8273-4539
Lincoln M P ShadeDepartment of Biostatistics, University of Kentucky, Lexington, KY, USA.
Daniel DiCorpoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Xueqiu JianGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-0313-6494
Donna K ArnettOffice of the Provost, University of South Carolina, Columbia, SC, USA.
Thomas R AustinCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
Alexa BeiserDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Joshua C BisCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3409-1110
John BlangeroDivision of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.ORCID http://orcid.org/0000-0001-6250-5723
Eric BoerwinkleDepartment of Epidemiology, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Jan BresslerDepartment of Epidemiology, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6578-4772
Joanne E CurranDivision of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.ORCID http://orcid.org/0000-0002-6898-155X
Charles S DeCarliDepartment of Neurology, University of California, Davis, CA, USA.ORCID http://orcid.org/0000-0003-1914-2693
Harsha DoddapaneniHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-2433-633X
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
David W FardoDepartment of Biostatistics, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0002-7207-4696
Jose C FlorezDiabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stacey GabrielGenomics Platform, Broad Institute, Cambridge, MA, USA.
Richard A GibbsHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
David C GlahnDepartment of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA.
Namrata GuptaGenomics Platform, Broad Institute, Cambridge, MA, USA.
Hector M GonzálezDepartment of Neurosciences and the Shiley-Marcos Alzheimer's Disease Research Center, University of California San Diego, San Diego, CA, USA.
Kevin A GonzálezDepartment of Neurosciences and the Shiley-Marcos Alzheimer's Disease Research Center, University of California San Diego, San Diego, CA, USA.
Konstantinos HatzikotoulasInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Kathleen M HaydenDepartment of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Susan R HeckbertCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7100-512X
Bertha HidalgoDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Alicia Huerta-ChagoyaPrograms in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Timothy M HughesDepartments of Internal Medicine and Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Charles L KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7986-8560
Lenore J LaunerLaboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-3238-7612
W T LongstrethDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
T2DGGI consortium
MAGIC consortium
Ravi MandlaPrograms in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Rasika A MathiasGeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Andrew P MorrisInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-6805-6014
Thomas H MosleyDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Ilya M NasrallahDepartment of Radiology, Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.
Paul NyquistDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Bruce M PsatyCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Qibin QiDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Laura M RaffieldDepartment of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-7892-193X
Nigel W RaynerInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.ORCID http://orcid.org/0000-0003-0510-4792
Alexander P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-1427-4470
Claudia L SatizabalGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-1115-4430
Elizabeth SelvinDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-6923-7151
Magdalena D R Sevilla-GonzalezPrograms in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6135-9998
Albert V SmithDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1942-5845
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3575-5468
Kirk SmithDiabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Beverly M SnivelyDepartment of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Lorraine SouthamInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Tamar SoferCardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8520-8860
Ken SuzukiDivision of Musculoskeletal and Dermatological Sciences, Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK.
Henry J TaylorCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2088-5240
Miriam S UdlerDiabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3824-9162
Karine A Viaud-MartinezIllumina Laboratory Services, Illumina, Inc., San Diego, CA, USA.ORCID http://orcid.org/0009-0001-0877-1358
Sylvia Wassertheil-SmollerDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.
Alexis C WoodUSDA/ARS Children Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
Lisa R YanekGeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-7117-1075
Xianyong YinDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Alisa K ManningPrograms in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0247-902X
Jerome I RotterDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0001-7191-1723
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
James B MeigsPrograms in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Myriam FornageDepartment of Epidemiology, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0003-0677-8158
Sudha SeshadriGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0001-6135-2622
Alanna C MorrisonDepartment of Epidemiology, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6381-4296
TOPMed Diabetes working group
and the TOPMed Neurocognitive working group
Funding
Therapeutic target discovery in ADSP data via comprehensive whole-genome analysis incorporating ethnic diversity and systems approachesU01AG058589 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ERIC A. BOERWINKLE, PHILIP L DE JAGER · 2022 to 2022
$5.1MThe San Antonio Heart and Mind StudyR01AG082360 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$3.5MUC Davis Alzheimer's Disease Research CenterP30AG072972 · UNIVERSITY OF CALIFORNIA AT DAVIS · 2025 to 2025
$3.2MSouth Texas Alzheimer's Disease Center Research and Education CoreP30AG066546 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$2.9MWorkforce Development CoreU54HG013247 · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · 2025 to 2025
$2.0MGenetic Architecture of Pure Alzheimer's Disease and Mixed PathologyR01AG082730 · UNIVERSITY OF WASHINGTON · 2025 to 2025
$1.0MMultiethnic Validation of VCID Biomarkers in South TexasU01NS125513 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$949kMentoring Investigators on the Clinical Translation of Cardiometabolic Genetic DiscoveriesK24HL157960 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$125kIntegration of dietary factors and multi-omic signatures of genetic subtypes to understand diabetes heterogeneityK99DK139461 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$90kNCATS NIH HHS KL2 TR002646NHGRI NIH HHS U54 HG013247NHLBI NIH HHS K24 HL157960NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL151855NHLBI NIH HHS U01 HL120393NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072972NIA NIH HHS R00 AG066849NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG059727NIA NIH HHS R01 AG082360NIA NIH HHS R01 AG082730NIA NIH HHS R21 AG075791NIA NIH HHS RF1 AG059421NIA NIH HHS U01 AG058589NIDDK NIH HHS K99 DK139461NINDS NIH HHS U01 NS125513
Abstract
To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P < 0.002) of the cross-population (P = 1.3 × 10
Indexed as
Insulin ResistanceAdultAgedCross-Sectional StudiesFemaleHumansMaleMetabolic SyndromeMiddle AgedPrecision Medicine
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