Genome-wide identification of DNA methylation QTLs in whole blood highlights pathways for cardiovascular disease.

Huan, Tianxiao; Joehanes, Roby; Song, Ci; Peng, Fen; Guo, Yichen; Mendelson, Michael; Yao, Chen; Liu, Chunyu; Ma, Jiantao; Richard, Melissa; Agha, Golareh; Guan, Weihua; Almli, Lynn M; Conneely, Karen N; Keefe, Joshua; Hwang, Shih-Jen; Johnson, Andrew D; Fornage, Myriam; Liang, Liming; Levy, Daniel

Huan, Tianxiao; Joehanes, Roby; Song, Ci; Peng, Fen; Guo, Yichen; Mendelson, Michael; Yao, Chen; Liu, Chunyu; Ma, Jiantao; Richard, Melissa; Agha, Golareh; Guan, Weihua; Almli, Lynn M; Conneely, Karen N; Keefe, Joshua; Hwang, Shih-Jen; Johnson, Andrew D; Fornage, Myriam; Liang, Liming; Levy, Daniel.

Affiliation

Huan T; The Framingham Heart Study, Framingham, MA, USA. tianxiao.huan@nih.gov.
Joehanes R; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. tianxiao.huan@nih.gov.
Song C; The Framingham Heart Study, Framingham, MA, USA.
Peng F; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Guo Y; The Framingham Heart Study, Framingham, MA, USA.
Mendelson M; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Yao C; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Liu C; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Ma J; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Richard M; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Agha G; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Guan W; The Framingham Heart Study, Framingham, MA, USA.
Almli LM; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Conneely KN; Department of Cardiology, Boston Children's Hospital, Harvard University, Boston, MA, USA.
Keefe J; The Framingham Heart Study, Framingham, MA, USA.
Hwang SJ; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Johnson AD; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Fornage M; The Framingham Heart Study, Framingham, MA, USA.
Liang L; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Levy D; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Nat Commun ; 10(1): 4267, 2019 09 19.

Article de En | MEDLINE | ID: mdl-31537805

ABSTRACT

ABSTRACT

Identifying methylation quantitative trait loci (meQTLs) and integrating them with disease-associated variants from genome-wide association studies (GWAS) may illuminate functional mechanisms underlying genetic variant-disease associations. Here, we perform GWAS of >415 thousand CpG methylation sites in whole blood from 4170 individuals and map 4.7 million cis- and 630 thousand trans-meQTL variants targeting >120 thousand CpGs. Independent replication is performed in 1347 participants from two studies. By linking cis-meQTL variants with GWAS results for cardiovascular disease (CVD) traits, we identify 92 putatively causal CpGs for CVD traits by Mendelian randomization analysis. Further integrating gene expression data reveals evidence of cis CpG-transcript pairs causally linked to CVD. In addition, we identify 22 trans-meQTL hotspots each targeting more than 30 CpGs and find that trans-meQTL hotspots appear to act in cis on expression of nearby transcriptional regulatory genes. Our findings provide a powerful meQTL resource and shed light on DNA methylation involvement in human diseases.

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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladies cardiovasculaires / Méthylation de l'ADN / Prédisposition génétique à une maladie / Locus de caractère quantitatif Type d'étude: Clinical_trials / Diagnostic_studies / Prognostic_studies Limites: Aged / Female / Humans / Male / Middle aged Langue: En Journal: Nat Commun Sujet du journal: BIOLOGIA / CIENCIA Année: 2019 Type de document: Article Pays d'affiliation: États-Unis d'Amérique

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