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  • Huan, TianxiaoFramingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA (author)

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

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-09-19
  • Springer Science and Business Media LLC,2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-395437
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-395437URI
  • https://doi.org/10.1038/s41467-019-12228-zDOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Joehanes, RobyFramingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA (author)
  • Song, CiUppsala universitet,Molekylär epidemiologi,Medicinsk genetik och genomik,Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, , Bethesda, MD USA(Swepub:uu)ciaso492 (author)
  • Peng, FenUniv Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, McGovern Med Sch, Houston, TX USA (author)
  • Guo, YichenHarvard Univ, Dept Environm Hlth, Harvard TH Chan Sch Publ Hlth, Boston, MA USA; Harvard Univ, Dept Biostat, Harvard TH Chan Sch Publ Hlth, Boston, MA USA (author)
  • Mendelson, MichaelFramingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA; Harvard Univ, Dept Cardiol, Boston Childrens Hosp, Boston, MA USA (author)
  • Yao, ChenFramingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA (author)
  • Liu, ChunyuBoston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA (author)
  • Ma, JiantaoFramingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA (author)
  • Richard, MelissaUniv Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, McGovern Med Sch, Houston, TX USA (author)
  • Agha, GolarehColumbia Univ, Mailman Sch Publ Hlth, New York, NY USA (author)
  • Guan, WeihuaUniv Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN USA (author)
  • Almli, Lynn M.Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA (author)
  • Conneely, Karen N.Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA (author)
  • Keefe, JoshuaFramingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA (author)
  • Hwang, Shih-JenFramingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA (author)
  • Johnson, Andrew D.Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA (author)
  • Fornage, MyriamUniv Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, McGovern Med Sch, Houston, TX USA (author)
  • Liang, LimingHarvard Univ, Dept Biostat, Harvard TH Chan Sch Publ Hlth, Boston, MA USA; Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA (author)
  • Leyy, DanielFramingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA (author)
  • Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USAMolekylär epidemiologi (creator_code:org_t)

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  • In:Nature Communications: Springer Science and Business Media LLC102041-1723

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