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Type 2 Diabetes Modifies the Association of CAD Genomic Risk Variants With Subclinical Atherosclerosis.
Hasbani, Natalie R; Westerman, Kenneth E; Kwak, Soo Heon; Chen, Han; Li, Xihao; Di Corpo, Daniel; Wessel, Jennifer; Bis, Joshua C; Sarnowski, Chloè; Wu, Peitao; Bielak, Lawrence F; Guo, Xiuqing; Heard-Costa, Nancy; Kinney, Gregory L; Mahaney, Michael C; Montasser, May E; Palmer, Nicholette D; Raffield, Laura M; Terry, James G; Yanek, Lisa R; Bon, Jessica; Bowden, Donald W; Brody, Jennifer A; Duggirala, Ravindranath; Jacobs, David R; Kalyani, Rita R; Lange, Leslie A; Mitchell, Braxton D; Smith, Jennifer A; Taylor, Kent D; Carson, April P; Curran, Joanne E; Fornage, Myriam; Freedman, Barry I; Gabriel, Stacey; Gibbs, Richard A; Gupta, Namrata; Kardia, Sharon L R; Kral, Brian G; Momin, Zeineen; Newman, Anne B; Post, Wendy S; Viaud-Martinez, Karine A; Young, Kendra A; Becker, Lewis C; Bertoni, Alain G; Blangero, John; Carr, John J; Pratte, Katherine; Psaty, Bruce M.
Affiliation
  • Hasbani NR; Department 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.).
  • Westerman KE; Department of Medicine, Clinical and Translation Epidemiology Unit (K.E.W., A.K.M.), Massachusetts General Hospital, Boston.
  • Kwak SH; Programs in Metabolism and Medical and Population Genetics (K.E.W., J.B.M., A.K.M.), Broad Institute, Cambridge.
  • Chen H; Department of Medicine, Harvard Medical School, Boston, MA (K.E.W., J.B.M., A.K.M.).
  • Li X; Department of Internal Medicine, Seoul National University Hospital, South Korea (S.H.K.).
  • Di Corpo D; Department 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.).
  • Wessel J; School of Biomedical Informatics, Center for Precision Health (H.C.), The University of Texas Health Science Center at Houston.
  • Bis JC; Department of Biostatistics, Harvard T.H. Chan School of Public Health (X. Li, X. Lin), Boston University School of Public Health, MA.
  • Sarnowski C; Department of Biostatistics (D.D., P.W.), Boston University School of Public Health, MA.
  • Wu P; Department of Epidemiology, Fairbanks School of Public Health, Indianapolis, IN (J.W.).
  • Bielak LF; Department of Medicine, Cardiovascular Health Research Unit (J.C.B., J.A.B., B.M.P.), University of Washington, Seattle.
  • Guo X; Department 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.).
  • Heard-Costa N; Department of Biostatistics (D.D., P.W.), Boston University School of Public Health, MA.
  • Kinney GL; Department of Medicine, Harvard Medical School, Boston, MA (K.E.W., J.B.M., A.K.M.).
  • Mahaney MC; Department 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.).
  • Montasser ME; Framingham Heart Study, MA (N.H.-C., R.S.V.).
  • Palmer ND; Department of Epidemiology, University of Colorado School of Public Health, Aurora (G.L.K., K.A.Y.).
  • Raffield LM; Department 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).
  • Terry JG; Department of Medicine, Division of Endocrinology Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore (M.E.M., B.D.M.).
  • Yanek LR; Department of Biochemistry (N.D.P., D.W.B.), Wake Forest School of Medicine, Winston-Salem, NC.
  • Bon J; Department of Genetics, University of North Carolina at Chapel Hill (L.M.R.).
  • Bowden DW; Department of Radiology, Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN (J.G.T., J.J.C.).
  • Brody JA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., R.R.K., B.G.K., L.C.B.).
  • Duggirala R; Department of Medicine, Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, PA (J. Bon).
  • Jacobs DR; Department of Biochemistry (N.D.P., D.W.B.), Wake Forest School of Medicine, Winston-Salem, NC.
  • Kalyani RR; Department of Medicine, Cardiovascular Health Research Unit (J.C.B., J.A.B., B.M.P.), University of Washington, Seattle.
  • Lange LA; Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, McAllen (R.D.).
  • Smith JA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., R.R.K., B.G.K., L.C.B.).
  • Taylor KD; Division of Biomedical Informatics and Personalized Medicine, School of Medicine University of Colorado, Aurora (L.A.L.).
  • Carson AP; Department of Medicine, Division of Endocrinology Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore (M.E.M., B.D.M.).
  • Curran JE; Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).
  • Fornage M; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor (L.F.B., J.A.S., S.L.R.K., P.A.P.).
  • Freedman BI; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor (J.A.S.).
  • Gabriel S; Department 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.).
  • Gibbs RA; Department of Medicine, University of Mississippi Medical Center, Jackson (A.P.C.).
  • Gupta N; Department 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).
  • Kardia SLR; Institute of Molecular Medicine (M.F.), The University of Texas Health Science Center at Houston.
  • Kral BG; Department of Internal Medicine, Section on Nephrology (B.I.F.), Wake Forest School of Medicine, Winston-Salem, NC.
  • Momin Z; Genomics Platform (S.G., N.G.), Broad Institute, Cambridge.
  • Newman AB; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX (R.A.G., Z.M.).
  • Post WS; Genomics Platform (S.G., N.G.), Broad Institute, Cambridge.
  • Viaud-Martinez KA; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor (L.F.B., J.A.S., S.L.R.K., P.A.P.).
  • Young KA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., R.R.K., B.G.K., L.C.B.).
  • Becker LC; Baylor College of Medicine Human Genome Sequencing Center, Houston, TX (R.A.G., Z.M.).
  • Bertoni AG; Department of Epidemiology, University of Pittsburgh School of Public Health, PA (A.B.N.).
  • Blangero J; Division of Cardiology, Johns Hopkins Medicine, Baltimore, MD (W.S.P.).
  • Carr JJ; Illumina Laboratory Services, Illumina, Inc, San Diego, CA (K.A.V.-M.).
  • Pratte K; Department of Epidemiology, University of Colorado School of Public Health, Aurora (G.L.K., K.A.Y.).
  • Psaty BM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., R.R.K., B.G.K., L.C.B.).
Circ Genom Precis Med ; 16(6): e004176, 2023 Dec.
Article in En | MEDLINE | ID: mdl-38014529
BACKGROUND: Individuals 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. METHODS: We 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. RESULTS: Using a Bonferroni-corrected significance threshold of P<1.6×10-4, we identified 3 genes (ATP1B1, ARVCF, and LIPG) associated with CAC and 2 genes (ABCG8 and EIF2B2) associated with carotid intima-media thickness and carotid plaque, respectively, through gene-based rare variant set analysis. Both ATP1B1 and ARVCF also had significantly different associations for CAC in T2D cases versus controls. No significant interaction tests were identified through the candidate single-variant analysis. CONCLUSIONS: These results highlight T2D as an important modifier of rare variant associations in CAD loci with CAC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Diabetes Mellitus, Type 2 / Atherosclerosis / Plaque, Atherosclerotic Limits: Humans Language: En Journal: Circ Genom Precis Med Year: 2023 Document type: Article Country of publication:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Diabetes Mellitus, Type 2 / Atherosclerosis / Plaque, Atherosclerotic Limits: Humans Language: En Journal: Circ Genom Precis Med Year: 2023 Document type: Article Country of publication: