Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

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Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease : A Mendelian Randomization Approach

Mendelson, Michael M. (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.;Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.

Marioni, Riccardo E. (författare): Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.

Joehanes, Roby (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA.

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Liu, Chunyu (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Boston Univ, Dept Biostat, Boston, MA USA.

Hedman, Åsa K (författare): Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab

Aslibekyan, Stella (författare): Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.

Demerath, Ellen W. (författare): Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.

Guan, Weihua (författare): Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.

Zhi, Degui (författare): Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA.

Yao, Chen (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.

Huan, Tianxiao (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.

Willinger, Christine (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.

Chen, Brian (författare): NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.

Courchesne, Paul (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.

Multhaup, Michael (författare): Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA.

Lrvin, Marguerite R. (författare): Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.

Cohain, Ariella (författare): Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.

Schadt, Eric E. (författare): Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.

Grove, Megan L. (författare): Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.

Bressler, Jan (författare): Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.

North, Kari (författare): Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA.

Sundström, Johan (författare): Uppsala universitet,Kardiologi

Gustafsson, Stefan (författare): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi

Shah, Sonia (författare): Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.

McRae, Allan F. (författare): Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.

Harris, Sarah E. (författare): Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland.

Gibson, Jude (författare): Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland.

Redmond, Paul (författare): Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland.

Coriey, Janie (författare): Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland.

Murphy, Lee (författare): Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland.

Starr, John M. (författare): Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland.

Kleinbrink, Erica (författare): Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA.

Lipovich, Leonard (författare): Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA.

Visscher, Peter M. (författare): Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.

Wray, Naomi R. (författare): Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.

Krauss, Ronald M. (författare): Childrens Hosp Oakland Res Inst, Oakland, CA USA.

Fallin, Daniele (författare): Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA.

Feinberg, Andrew (författare): Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA.

Absher, Devin M. (författare): HudsonAlpha Inst Biotechnol, Huntsville, AL USA.

Fornage, Myriam (författare): Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Univ Texas Houston, Brown Fdn Inst Mol Med, Houston, TX USA.

Pankow, James S. (författare): Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.

Lind, Lars (författare): Uppsala universitet,Kardiovaskulär epidemiologi

Fox, Caroline (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.

Ingelsson, Erik (författare): Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.

Arnett, Donna K. (författare): Univ Kentucky, Coll Publ Hlth, Lexington, KY USA.

Boerwinkle, Eric (författare): Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.

Liang, Liming (författare): Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.

Levy, Daniel (författare): Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.

Deary, Lan J. (författare): Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland.

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Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;Boston Univ, Sch Med, Boston, MA 02118 USA.;Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA. Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. (creator_code:org_t)

PUBLIC LIBRARY SCIENCE, 2017
2017
Engelska.
Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:1

Relaterad länk:: https://uu.diva-port... (primary) (Raw object); visa fler...; https://urn.kb.se/re...; visa färre...

Tidskriftsartikel (refereegranskat)

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Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.

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Av författaren/redakt...: Mendelson, Micha ...; Marioni, Riccard ...; Joehanes, Roby; Liu, Chunyu; Hedman, Åsa K; Aslibekyan, Stel ...; visa fler...; Demerath, Ellen ...; Guan, Weihua; Zhi, Degui; Yao, Chen; Huan, Tianxiao; Willinger, Chris ...; Chen, Brian; Courchesne, Paul; Multhaup, Michae ...; Lrvin, Marguerit ...; Cohain, Ariella; Schadt, Eric E.; Grove, Megan L.; Bressler, Jan; North, Kari; Sundström, Johan; Gustafsson, Stef ...; Shah, Sonia; McRae, Allan F.; Harris, Sarah E.; Gibson, Jude; Redmond, Paul; Coriey, Janie; Murphy, Lee; Starr, John M.; Kleinbrink, Eric ...; Lipovich, Leonar ...; Visscher, Peter ...; Wray, Naomi R.; Krauss, Ronald M ...; Fallin, Daniele; Feinberg, Andrew; Absher, Devin M.; Fornage, Myriam; Pankow, James S.; Lind, Lars; Fox, Caroline; Ingelsson, Erik; Arnett, Donna K.; Boerwinkle, Eric; Liang, Liming; Levy, Daniel; Deary, Lan J.; visa färre...

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Av lärosätet: Uppsala universitet

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Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease : A Mendelian Randomization Approach

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