Maria Grau-Perez1,2,3, Golareh Agha4, Yuanjie Pang5, Jose D Bermudez6, Maria Tellez-Plaza7,8,9. 1. Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Av. Menendez Pelayo 4 accesorio, 46010, Valencia, Spain. graupema@alumni.uv.es. 2. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY, 10032, USA. graupema@alumni.uv.es. 3. Department of Statistics and Operational Research, University of Valencia, Av. Dr. Moliner 50, Valencia, Burjassot, 46100, Spain. graupema@alumni.uv.es. 4. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY, 10032, USA. 5. Clinical Trial Service Unit & Epidemiological Studies (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. 6. Department of Statistics and Operational Research, University of Valencia, Av. Dr. Moliner 50, Valencia, Burjassot, 46100, Spain. 7. Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Av. Menendez Pelayo 4 accesorio, 46010, Valencia, Spain. 8. Department of Chronic Diseases Epidemiology, National Center for Epidemiology, National Institutes for Health Carlos III, C/ Monforte de Lemos, 5. Pabellón 12, 28029, Madrid, Spain. 9. Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA.
Abstract
PURPOSE OF REVIEW: Epigenetic modifications are environmentally responsive and may play a mechanistic role in the development of disease. Mendelian randomization uses genetic variation to assess the causal effect of modifiable exposures on health outcomes. We conducted a systematic review of Mendelian randomization studies evaluating the causal role of DNA methylation (DNAm) changes on the development of health states, emphasizing on studies that formally evaluate exposure-DNAm, in addition to DNAm-outcome, causal associations. RECENT FINDINGS: We identified 15 articles, 4 of them including an environmental determinant of DNAm, including self-reported tobacco smoke exposure, in utero tobacco smoke exposure, measured vitamin B12, and glycemia. Selected articles suggest a causal association of DNAm with some cardiometabolic endpoints. DNAm seemed to partly explain the association of postnatal and prenatal exposure to tobacco smoke and vitamin B12 with inflammation biomarkers, birth weight, and cognitive outcomes, respectively. However, the current evidence is not sufficient to infer causality. Additional Mendelian randomization studies from large epidemiologic samples are needed to support the causal role of environmental factors as determinants of health-related epigenetic modifications.
PURPOSE OF REVIEW: Epigenetic modifications are environmentally responsive and may play a mechanistic role in the development of disease. Mendelian randomization uses genetic variation to assess the causal effect of modifiable exposures on health outcomes. We conducted a systematic review of Mendelian randomization studies evaluating the causal role of DNA methylation (DNAm) changes on the development of health states, emphasizing on studies that formally evaluate exposure-DNAm, in addition to DNAm-outcome, causal associations. RECENT FINDINGS: We identified 15 articles, 4 of them including an environmental determinant of DNAm, including self-reported tobacco smoke exposure, in utero tobacco smoke exposure, measured vitamin B12, and glycemia. Selected articles suggest a causal association of DNAm with some cardiometabolic endpoints. DNAm seemed to partly explain the association of postnatal and prenatal exposure to tobacco smoke and vitamin B12 with inflammation biomarkers, birth weight, and cognitive outcomes, respectively. However, the current evidence is not sufficient to infer causality. Additional Mendelian randomization studies from large epidemiologic samples are needed to support the causal role of environmental factors as determinants of health-related epigenetic modifications.
Entities:
Keywords:
DNA methylation; Environmental; Health outcomes; Mendelian randomization; Systematic review
Authors: Jeffrey T Leek; Robert B Scharpf; Héctor Corrada Bravo; David Simcha; Benjamin Langmead; W Evan Johnson; Donald Geman; Keith Baggerly; Rafael A Irizarry Journal: Nat Rev Genet Date: 2010-09-14 Impact factor: 53.242
Authors: Roby Joehanes; Allan C Just; Riccardo E Marioni; Luke C Pilling; Lindsay M Reynolds; Pooja R Mandaviya; Weihua Guan; Tao Xu; Cathy E Elks; Stella Aslibekyan; Hortensia Moreno-Macias; Jennifer A Smith; Jennifer A Brody; Radhika Dhingra; Paul Yousefi; James S Pankow; Sonja Kunze; Sonia H Shah; Allan F McRae; Kurt Lohman; Jin Sha; Devin M Absher; Luigi Ferrucci; Wei Zhao; Ellen W Demerath; Jan Bressler; Megan L Grove; Tianxiao Huan; Chunyu Liu; Michael M Mendelson; Chen Yao; Douglas P Kiel; Annette Peters; Rui Wang-Sattler; Peter M Visscher; Naomi R Wray; John M Starr; Jingzhong Ding; Carlos J Rodriguez; Nicholas J Wareham; Marguerite R Irvin; Degui Zhi; Myrto Barrdahl; Paolo Vineis; Srikant Ambatipudi; André G Uitterlinden; Albert Hofman; Joel Schwartz; Elena Colicino; Lifang Hou; Pantel S Vokonas; Dena G Hernandez; Andrew B Singleton; Stefania Bandinelli; Stephen T Turner; Erin B Ware; Alicia K Smith; Torsten Klengel; Elisabeth B Binder; Bruce M Psaty; Kent D Taylor; Sina A Gharib; Brenton R Swenson; Liming Liang; Dawn L DeMeo; George T O'Connor; Zdenko Herceg; Kerry J Ressler; Karen N Conneely; Nona Sotoodehnia; Sharon L R Kardia; David Melzer; Andrea A Baccarelli; Joyce B J van Meurs; Isabelle Romieu; Donna K Arnett; Ken K Ong; Yongmei Liu; Melanie Waldenberger; Ian J Deary; Myriam Fornage; Daniel Levy; Stephanie J London Journal: Circ Cardiovasc Genet Date: 2016-09-20
Authors: Rebecca C Richmond; Gemma C Sharp; Mary E Ward; Abigail Fraser; Oliver Lyttleton; Wendy L McArdle; Susan M Ring; Tom R Gaunt; Debbie A Lawlor; George Davey Smith; Caroline L Relton Journal: Diabetes Date: 2016-02-09 Impact factor: 9.461
Authors: Eugene Andres Houseman; William P Accomando; Devin C Koestler; Brock C Christensen; Carmen J Marsit; Heather H Nelson; John K Wiencke; Karl T Kelsey Journal: BMC Bioinformatics Date: 2012-05-08 Impact factor: 3.169