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Elucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease.
Ma, Jiantao; Joehanes, Roby; Liu, Chunyu; Keshawarz, Amena; Hwang, Shih-Jen; Bui, Helena; Tejada, Brandon; Sooda, Meera; Munson, Peter J; Demirkale, Cumhur Y; Courchesne, Paul; Heard-Costa, Nancy L; Pitsillides, Achilleas N; Feolo, Mike; Sharopova, Nataliya; Vasan, Ramachandran S; Huan, Tianxiao; Levy, Daniel.
  • Ma J; Division of Nutrition Epidemiology and Data Science, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA. jiantao.ma@tufts.edu.
  • Joehanes R; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Liu C; Framingham Heart Study, Framingham, MA, USA.
  • Keshawarz A; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
  • Hwang SJ; Boston University, Boston, MA, USA.
  • Bui H; National Heart, Lung, and Blood Institute, Framingham Heart Study, Framingham, MA, USA.
  • Tejada B; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Sooda M; Framingham Heart Study, Framingham, MA, USA.
  • Munson PJ; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Demirkale CY; Framingham Heart Study, Framingham, MA, USA.
  • Courchesne P; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Heard-Costa NL; Framingham Heart Study, Framingham, MA, USA.
  • Pitsillides AN; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Feolo M; Framingham Heart Study, Framingham, MA, USA.
  • Sharopova N; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Vasan RS; Framingham Heart Study, Framingham, MA, USA.
  • Huan T; Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Levy D; Framingham Heart Study, Framingham, MA, USA.
Sci Rep ; 12(1): 19564, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2119334
ABSTRACT
DNA methylation commonly occurs at cytosine-phosphate-guanine sites (CpGs) that can serve as biomarkers for many diseases. We analyzed whole genome sequencing data to identify DNA methylation quantitative trait loci (mQTLs) in 4126 Framingham Heart Study participants. Our mQTL mapping identified 94,362,817 cis-mQTLvariant-CpG pairs (for 210,156 unique autosomal CpGs) at P < 1e-7 and 33,572,145 trans-mQTL variant-CpG pairs (for 213,606 unique autosomal CpGs) at P < 1e-14. Using cis-mQTL variants for 1258 CpGs associated with seven cardiovascular disease (CVD) risk factors, we found 104 unique CpGs that colocalized with at least one CVD trait. For example, cg11554650 (PPP1R18) colocalized with type 2 diabetes, and was driven by a single nucleotide polymorphism (rs2516396). We performed Mendelian randomization (MR) analysis and demonstrated 58 putatively causal relations of CVD risk factor-associated CpGs to one or more risk factors (e.g., cg05337441 [APOB] with LDL; MR P = 1.2e-99, and 17 causal associations with coronary artery disease (e.g. cg08129017 [SREBF1] with coronary artery disease; MR P = 5e-13). We also showed that three CpGs, e.g., cg14893161 (PM20D1), are putatively causally associated with COVID-19 severity. To assist in future analyses of the role of DNA methylation in disease pathogenesis, we have posted a comprehensive summary data set in the National Heart, Lung, and Blood Institute's BioData Catalyst.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronary Artery Disease / Diabetes Mellitus, Type 2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-24100-0

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronary Artery Disease / Diabetes Mellitus, Type 2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-24100-0