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

Huan, Tianxiao (author)
Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA
Joehanes, Roby (author)
Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA
Song, Ci (author)
Uppsala 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
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Peng, Fen (author)
Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, McGovern Med Sch, Houston, TX USA
Guo, Yichen (author)
Harvard 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
Mendelson, Michael (author)
Framingham 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
Yao, Chen (author)
Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA
Liu, Chunyu (author)
Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA
Ma, Jiantao (author)
Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA
Richard, Melissa (author)
Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, McGovern Med Sch, Houston, TX USA
Agha, Golareh (author)
Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA
Guan, Weihua (author)
Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN USA
Almli, Lynn M. (author)
Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA
Conneely, Karen N. (author)
Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA
Keefe, Joshua (author)
Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA
Hwang, Shih-Jen (author)
Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA
Johnson, Andrew D. (author)
Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA
Fornage, Myriam (author)
Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Brown Fdn, McGovern Med Sch, Houston, TX USA
Liang, Liming (author)
Harvard Univ, Dept Biostat, Harvard TH Chan Sch Publ Hlth, Boston, MA USA; Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
Leyy, Daniel (author)
Framingham Heart Dis Epidemiol Study, Framingham, MA USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD USA
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 (creator_code:org_t)
2019-09-19
2019
English.
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
Related links:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
https://www.nature.c...
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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