ArticleCirculation. Genomic and precision medicine2023
Type 2 Diabetes Modifies the Association of CAD Genomic Risk Variants With Subclinical Atherosclerosis.
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Article in Circulation. Genomic and precision medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3citing papers in PubMed
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Who cites it
3 citing papers in PubMed, 9 citations in OpenAlex.
- The changing epidemiology of human type 2 diabetes-associated atherosclerosis: Pathophysiological mechanisms and emerging treatment possibilities.Journal of internal medicine · 2026Review
- The Role of Obesity as a Cardiac Disease Risk Factor in Patients with Type 2 Diabetes.Current cardiology reports · 2024Review
- Enhancing prediction accuracy of coronary artery disease through machine learning-driven genomic variant selection.Journal of translational medicine · 2024Article
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Authors and funding
62 authors at 20 institutions in 7 countries.
Natalie R HasbaniDepartment of Epidemiology Human Genetics and Environmental Sciences, Human Genetics Center, The University of Texas Health Science Center at Houston School of Public Health (N.R.H., H.C., C.S., A.C.M., P.S.d.V.).
Kenneth E WestermanDepartment of Medicine, Clinical and Translation Epidemiology Unit (K.E.W., A.K.M.), Massachusetts General Hospital, Boston.ORCID 0000-0001-7619-1868
Soo Heon KwakDepartment of Internal Medicine, Seoul National University Hospital, South Korea (S.H.K.).
Han ChenDepartment of Epidemiology Human Genetics and Environmental Sciences, Human Genetics Center, The University of Texas Health Science Center at Houston School of Public Health (N.R.H., H.C., C.S., A.C.M., P.S.d.V.).ORCID 0000-0002-9510-4923
Xihao LiDepartment of Biostatistics, Harvard T.H. Chan School of Public Health (X. Li, X. Lin), Boston University School of Public Health, MA.ORCID 0000-0001-8151-0106
Daniel Di CorpoDepartment of Biostatistics (D.D., P.W.), Boston University School of Public Health, MA.
Jennifer WesselDepartment of Epidemiology, Fairbanks School of Public Health, Indianapolis, IN (J.W.).ORCID 0000-0002-7031-0085
Joshua C BisDepartment of Medicine, Cardiovascular Health Research Unit (J.C.B., J.A.B., B.M.P.), University of Washington, Seattle.ORCID 0000-0002-3409-1110
Chloè SarnowskiDepartment of Epidemiology Human Genetics and Environmental Sciences, Human Genetics Center, The University of Texas Health Science Center at Houston School of Public Health (N.R.H., H.C., C.S., A.C.M., P.S.d.V.).
Peitao WuDepartment of Biostatistics (D.D., P.W.), Boston University School of Public Health, MA.
Lawrence F BielakDepartment of Medicine, Harvard Medical School, Boston, MA (K.E.W., J.B.M., A.K.M.).ORCID 0000-0002-3443-8030
Xiuqing GuoDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-University of California Los Angeles Medical Center, Torrance (X.G., K.D.T.).ORCID 0000-0002-5264-5068
Nancy Heard-CostaFramingham Heart Study, MA (N.H.-C., R.S.V.).ORCID 0000-0001-9730-0306
Gregory L KinneyDepartment of Epidemiology, University of Colorado School of Public Health, Aurora (G.L.K., K.A.Y.).ORCID 0000-0002-5218-4986
Michael C MahaneyDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville (M.C.M., J.E.C., J. Blangero).ORCID 0000-0002-1341-3950
May E MontasserDepartment of Medicine, Division of Endocrinology Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore (M.E.M., B.D.M.).ORCID 0000-0002-9558-5456
Nicholette D PalmerDepartment of Biochemistry (N.D.P., D.W.B.), Wake Forest School of Medicine, Winston-Salem, NC.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill (L.M.R.).
James G TerryDepartment of Radiology, Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN (J.G.T., J.J.C.).ORCID 0000-0001-6659-3441
Lisa R YanekDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., R.R.K., B.G.K., L.C.B.).ORCID 0000-0001-7117-1075
Jessica BonDepartment of Medicine, Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, PA (J. Bon).ORCID 0000-0002-4336-3835
Donald W BowdenDepartment of Biochemistry (N.D.P., D.W.B.), Wake Forest School of Medicine, Winston-Salem, NC.
Jennifer A BrodyDepartment of Medicine, Cardiovascular Health Research Unit (J.C.B., J.A.B., B.M.P.), University of Washington, Seattle.ORCID 0000-0001-8509-148X
Ravindranath DuggiralaDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, McAllen (R.D.).
David R JacobsORCID 0000-0002-7232-0543
Rita R KalyaniDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., R.R.K., B.G.K., L.C.B.).
Leslie A LangeDivision of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado, Aurora (L.A.L.).
Braxton D MitchellDepartment of Medicine, Division of Endocrinology Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore (M.E.M., B.D.M.).ORCID 0000-0003-4920-4744
Jennifer A SmithDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor (L.F.B., J.A.S., S.L.R.K., P.A.P.).ORCID 0000-0002-3575-5468
Kent D TaylorDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-University of California Los Angeles Medical Center, Torrance (X.G., K.D.T.).ORCID 0000-0002-2756-4370
April P CarsonDepartment of Medicine, University of Mississippi Medical Center, Jackson (A.P.C.).ORCID 0000-0002-7970-6756
Joanne E CurranDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville (M.C.M., J.E.C., J. Blangero).ORCID 0000-0002-6898-155X
Myriam FornageInstitute of Molecular Medicine (M.F.), The University of Texas Health Science Center at Houston.ORCID 0000-0003-0677-8158
Barry I FreedmanDepartment of Internal Medicine, Section on Nephrology (B.I.F.), Wake Forest School of Medicine, Winston-Salem, NC.ORCID 0000-0003-0275-5530
Stacey GabrielGenomics Platform (S.G., N.G.), Broad Institute, Cambridge.
Richard A GibbsBaylor College of Medicine Human Genome Sequencing Center, Houston, TX (R.A.G., Z.M.).
Namrata GuptaGenomics Platform (S.G., N.G.), Broad Institute, Cambridge.ORCID 0000-0001-6786-4995
Sharon L R KardiaDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor (L.F.B., J.A.S., S.L.R.K., P.A.P.).
Brian G KralDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., R.R.K., B.G.K., L.C.B.).ORCID 0000-0001-9493-2084
Zeineen MominBaylor College of Medicine Human Genome Sequencing Center, Houston, TX (R.A.G., Z.M.).ORCID 0000-0001-7646-2234
Anne B NewmanDepartment of Epidemiology, University of Pittsburgh School of Public Health, PA (A.B.N.).ORCID 0000-0002-0106-1150
Wendy S PostDivision of Cardiology, Johns Hopkins Medicine, Baltimore, MD (W.S.P.).ORCID 0000-0002-8655-5204
Karine A Viaud-MartinezIllumina Laboratory Services, Illumina, Inc, San Diego, CA (K.A.V.-M.).
Kendra A YoungDepartment of Epidemiology, University of Colorado School of Public Health, Aurora (G.L.K., K.A.Y.).
Lewis C BeckerDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., R.R.K., B.G.K., L.C.B.).ORCID 0000-0003-4805-3403
Alain G BertoniEpidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC (A.G.B.).ORCID 0000-0002-7503-6273
John BlangeroDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville (M.C.M., J.E.C., J. Blangero).ORCID 0000-0001-6250-5723
John J CarrDepartment of Radiology, Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN (J.G.T., J.J.C.).
Katherine PratteDepartment of Biostatistics, National Jewish Health, Denver, CO (K.P.).
Bruce M PsatyDepartment of Medicine, Cardiovascular Health Research Unit (J.C.B., J.A.B., B.M.P.), University of Washington, Seattle.ORCID 0000-0002-7278-2190
Stephen S RichORCID 0000-0003-3872-7793
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; TOPMed Atherosclerosis Working Group; TOPMed Diabetes Working Group
Joseph C WuCenter for Public Health Genomics, University of Virginia School of Medicine, Charlottesville (J.C.W.).ORCID 0000-0002-6068-8041
Rajeev MalhotraDivision of Cardiology (R.M.), Massachusetts General Hospital, Boston.ORCID 0000-0003-0120-4630
Patricia A PeyserDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor (L.F.B., J.A.S., S.L.R.K., P.A.P.).ORCID 0000-0002-9717-8459
Alanna C MorrisonDepartment of Epidemiology Human Genetics and Environmental Sciences, Human Genetics Center, The University of Texas Health Science Center at Houston School of Public Health (N.R.H., H.C., C.S., A.C.M., P.S.d.V.).ORCID 0000-0001-6381-4296
Ramachandran S VasanFramingham Heart Study, MA (N.H.-C., R.S.V.).ORCID 0000-0001-7357-5970
Xihong LinDepartment of Biostatistics, Harvard T.H. Chan School of Public Health (X. Li, X. Lin), Boston University School of Public Health, MA.ORCID 0000-0001-7067-7752
Jerome I RotterORCID 0000-0001-7191-1723
James B MeigsDivision of General Internal Medicine (J.B.M.), Massachusetts General Hospital, Boston.
Alisa K ManningDepartment of Medicine, Clinical and Translation Epidemiology Unit (K.E.W., A.K.M.), Massachusetts General Hospital, Boston.ORCID 0000-0003-0247-902X
Paul S de VriesDepartment of Epidemiology Human Genetics and Environmental Sciences, Human Genetics Center, The University of Texas Health Science Center at Houston School of Public Health (N.R.H., H.C., C.S., A.C.M., P.S.d.V.).ORCID 0000-0003-0964-0111
Broad Institute · USJohns Hopkins University · USThe University of Texas Health Science Center at Houston · USThe University of Texas Rio Grande Valley · USWake Forest University · USHarvard University · USUniversity of Michigan · USBaylor College of Medicine · USBoston University · USColorado School of Public Health · USLos Angeles Biomedical Research Institute · USPinchot University · USUniversity of Maryland, Baltimore · USVanderbilt University Medical Center · USCardiovascular Institute of the South · USFramingham Heart Study · USIllumina (United States) · USJacobs (United States) · USMassachusetts General Hospital · USMettler-Toledo (Switzerland) · CH
Funding
PEDIGREE ANALYSIS OF LIPOPROTEIN PHENOTYPESP01HL045522 · NHLBI · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI BLANGERO, JOHN · 1991 to 2012
$27.6MWorkforce Development CoreU54HG013247 · NHGRI · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI Gladys E. Maestre · 2023 to 2026
$10.5MStudies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MWhole Genome Sequencing to Identify Causal Genetic Variants Influencing CVD RiskR01HL113323 · NHLBI · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI BLANGERO, JOHN, CURRAN, JOANNE E. · 2012 to 2016
$8.2MRare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6MAnalysis of Whole Genome Sequence and Hemostasis PhenotypesR01HL139553 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI PAUL STEFAN DE VRIES, Alanna C Morrison · 2018 to 2026
$5.0MMethods and Software for Large-Scale Gene-Environment Interaction StudiesR01HL145025 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI CHEN, HAN, MANNING, ALISA KNODLE · 2019 to 2023
$4.0MThe Role of Histone Deacetylase 9 in Vascular CalcificationR01HL142809 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MALHOTRA, RAJEEV · 2018 to 2022
$4.0MWhole-genome sequencing analysis of coronary atherosclerosis and related traitsR01HL146860 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI DE VRIES, PAUL STEFAN · 2020 to 2024
$3.9MTOPMed Omics of Type 2 Diabetes and Quantitative TraitsUM1DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MANNING, ALISA KNODLE · 2021 to 2025
$3.8MNHGRI NIH HHS U54 HG013247NHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS P01 HL045522NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL113323NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL139553NHLBI NIH HHS R01 HL142809NHLBI NIH HHS R01 HL145025NHLBI NIH HHS R01 HL146860NHLBI NIH HHS R01 HL151855NHLBI NIH HHS R01 HL159514NHLBI NIH HHS U01 HL120393NIA NIH HHS K99 AG066849NIA NIH HHS R00 AG066849NIDDK NIH HHS K01 DK133637NIDDK NIH HHS R01 DK127636NIDDK NIH HHS UM1 DK078616
Abstract
backgroundIndividuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.
methodsWe compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program. We included first-order T2D interaction terms in each model to determine whether CAD loci were modified by T2D. The genetic main and interaction effects were assessed using a joint test to determine whether a CAD variant, or gene-based rare variant set, was associated with the respective subclinical atherosclerosis measures and then further determined whether these loci had a significant interaction test.
resultsUsing a Bonferroni-corrected significance threshold of
conclusionsThese results highlight T2D as an important modifier of rare variant associations in CAD loci with CAC.
Indexed as
AtherosclerosisCoronary Artery DiseaseDiabetes Mellitus, Type 2Plaque, AtheroscleroticCarotid Intima-Media ThicknessGenomicsHumansRisk Factorsatherosclerosiscoronary artery diseasediabCs, type 2geneticsrisk factors
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