Mendelian randomization: Applications and limitations in epigenetic studies

Epigenomics

Volumn 7, Issue 8, 2015, Pages 1239-1243

  Relton, Caroline L ^a   Davey Smith, George ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

Causal inference; DNA methylation; epidemiology; epigenetics; mediation; SNP

Indexed keywords

DNA;

ALZHEIMER DISEASE; BLOOD PRESSURE; DNA METHYLATION; ENVIRONMENTAL EXPOSURE; EPIGENETICS; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; MENDELIAN RANDOMIZATION ANALYSIS; NOTE; PARKINSON DISEASE; PRIORITY JOURNAL; QUANTITATIVE TRAIT LOCUS; SINGLE NUCLEOTIDE POLYMORPHISM; GENETIC EPIGENESIS; GENETIC VARIATION;

EPIGENESIS, GENETIC; EPIGENOMICS; GENETIC VARIATION; HUMANS; MENDELIAN RANDOMIZATION ANALYSIS;

EID: 84950268824     PISSN: 17501911     EISSN: 1750192X     Source Type: Journal    
DOI: 10.2217/epi.15.88     Document Type: Note

References (31)

1. Mathers JC, Strathdee G, Relton CL. Induction of epigenetic alterations by dietary and other environmental factors. Adv. Genet. 71, 3-39 (2010).
2. Cortessis VK1, Thomas DC, Levine AJ et al. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum. Genet. 131, 1565-1589 (2012).
3. Barrow TM, Michels KB. Epigenetic epidemiology of cancer. Biochem. Biophys. Res. Commun. 455, 70-83 (2014).
4. Urdinguio RG, Sanchez-Mut JV, Esteller M. Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol. 8, 1056-1072 (2009).
5. Dick KJ, Nelson CP, Tsaprouni L et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet 383, 1990-1998 (2014).
6. Liang L, Willis-Owen SA, Laprise C et al. An epigenome-wide association study of total serum immunoglobulin E concentration. Nature 520(7549), 670-674 (2015).
7. Davey Smith G, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease Int. J. Epidemiol. 32, 1-22 (2003).
8. Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum. Mol. Genet. 23(R1), R89-R98 (2014).
9. Greenland S. An introduction to instrumental variables for epidemiologists. Int. J. Epidemiol. 29, 722-729 (2000).
10. Sheehan NA, Didelez V, Burton PR, Tobin MD. Mendelian randomisation and causal inference in observational epidemiology. PLoS Med. 5, e177 (2008).
11. Jansen RC, Nap JP. Genetical genomics: the added value from segregation. Trends Genet. 17, 388-391 (2001).
12. Schadt EE, Lamb J, Yang X et al. An integrative genomics approach to infer causal associations between gene expression and disease. Nat. Genet. 37, 710-717 (2005).
13. Liu Y, Aryee MJ, Padyukov L et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat. Biotechnol. 31, 142-147 (2013).
14. Blakely T, McKenzie S, Carter K. Misclassification of the mediator matters when estimating indirect effects. J. Epidemiol. Community Health 67, 458-466 (2013).
15. Relton CL, Davey Smith G. Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int. J. Epidemiol. 41, 161-176 (2012).
16. Zhang D, Cheng L, Badner JA et al. Genetic control of individual differences in gene-specific methylation in human brain. Am. J. Hum. Genet. 86, 411-419 (2010).
17. Bell JT, Pai AA, Pickrell JK et al. DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol. 12, R10 (2011).
18. Timofeeva MN, McKay JD, Davey Smith G et al. Genetic Polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC. Cancer Epidemiol. Biomarkers Prev. 20, 2250-2261 (2011).
19. Zuccolo L, Fitz-Simon N, Gray R et al. A non-synonymous variant in ADH1B is strongly associated with prenatal alcohol use in a European sample of pregnant women. Hum. Mol. Genet. 18, 4457-4466 (2009).
20. Timpson NJ, Harbord R, Davey Smith G, Zacho J, Tybjaerg-Hansen A, Nordestgaard BG. Does greater adiposity increase blood pressure and hypertension risk Mendelian randomization using the FTO/MC4R genotype. Hypertension 54, 84-90 (2009).
21. Benn M, Tybjaerg-Hansen A, Stender S, Frikke-Schmidt R, Nordestgaard BG. Low-density lipoprotein cholesterol and the risk of cancer: a Mendelian randomization study. J. Natl Cancer Inst. 103, 508-519 (2011).
22. Rakyan VK, Down TA, Balding DJ, Beck S. Epigenome-wide association studies for common human diseases. Nat. Rev. Genet. 12, 529-541 (2011).
23. Shi J, Marconett CN, Duan J et al. Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue. Nat. Commun. 5, 3365 (2014).
24. Cole DA, Preacher KJ. Manifest variable path analysis: potentially serious and misleading consequences due to uncorrected measurement error. Psychol. Methods 19, 300-315 (2014).
25. Groom A, Potter C, Swan DC et al. Postnatal growth and DNA methylation are associated with differential gene expression of the TACSTD2 gene and childhood fat mass. Diabetes 61, 391-400 (2012).
26. Allard C, Desgagne V, Patenaude J et al. Mendelian randomization supports causality between maternal hyperglycaemia and epigenetic regulation of leptin gene in newborns. Epigenetics 10(4), 342-351 (2015).
27. Kirkbride J, Susser E, Kundakovic M, Kresovich JK, Davey Smith G, Relton CL. Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects Epigenomics 4(3), 303-315 (2012).
28. Terry MB, Delgado-Cruzata L, Vin-Raviv N, Wu HC, Santella RM. DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics 6, 828-837 (2011).
29. Zeilinger S, Kühnel B, Klopp N et al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS ONE 8, e63812 (2013).
30. Maher B. ENCODE: the human encyclopaedia. Nature 489, 46-48 (2012).
31. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int. J. Epidemiol. 44(2), 512-525 (2015).