Epigenetics and human obesity

International Journal of Obesity

Volumn 39, Issue 1, 2015, Pages 85-97

  Van Dijk, S J ^a   Molloy, P L ^a   Varinli, H ^a,b,c   Morrison, J L ^d   Muhlhausler, B S ^e,f   Buckley, M ^a   Clark, S J ^c   McMillen, I C ^d   Noakes, M ^a   Samaras, K ^g   Tellam, R L ^a  

^a CSIRO   (Australia)

^b MACQUARIE UNIVERSITY   (Australia)

^c GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^d UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

^e UNIVERSITY OF ADELAIDE   (Australia)

^f CHILD HEALTH RESEARCH INSTITUTE   (Australia)

^g ST VINCENT S HOSPITAL   (Australia)

Author keywords

adipose tissue; developmental programming; DNA methylation; epigenetics

Indexed keywords

ADIPOSE TISSUE; BLOOD CELL; DNA METHYLATION; EPIGENETICS; GENETIC ASSOCIATION; HUMAN; OBESITY; PERINATAL PERIOD; PRENATAL PERIOD; REVIEW; RISK ASSESSMENT; SYSTEMATIC REVIEW; CARDIOVASCULAR DISEASES; CROSS-SECTIONAL STUDY; DIABETES MELLITUS, TYPE 2; ENVIRONMENTAL EXPOSURE; GENETICS; HEALTH; LIFESTYLE; LONGITUDINAL STUDY; PATHOPHYSIOLOGY; WEIGHT REDUCTION;

CARDIOVASCULAR DISEASES; CROSS-SECTIONAL STUDIES; DIABETES MELLITUS, TYPE 2; DNA METHYLATION; ENVIRONMENTAL EXPOSURE; EPIGENOMICS; GLOBAL HEALTH; HUMANS; LIFE STYLE; LONGITUDINAL STUDIES; OBESITY; WEIGHT LOSS;

EID: 84920672944     PISSN: 03070565     EISSN: 14765497     Source Type: Journal    
DOI: 10.1038/ijo.2014.34     Document Type: Review

References (123)

1. WHO. Overweight and obesity. Available from: www.who.int/gho/ncd/risk-factors/overweight/en/index.html.
2. Kopelman P. Health risks associated with overweight and obesity. Obes Rev 2007; 8: 13-17.
3. Hafekost K, Lawrence D, Mitrou F, O'Sullivan TA, Zubrick SR. Tackling overweight and obesity: does the public health message match the science? BMC Med 2013; 11: 41.
4. Gortmaker SL, Swinburn BA, Levy D, Carter R, Mabry PL, Finegood DT et al. Changing the future of obesity: science, policy, and action. Lancet 2011; 378: 838-847.
5. Gillman MW, Ludwig DS. How early should obesity prevention start? N Engl J Med 2013; 369: 1-3.
6. Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr 2007; 27: 363-388.
7. Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet 1996; 30: 441-464.
8. Arimondo P, Egger G, Tost J, How Kit A, Nielsen HM, Tost J. DNA methylation based biomarkers: practical considerations and applications. Biochimie 2012; 94: 2314-2337.
9. Jufvas A, Sjödin S, Lundqvist K, Amin R, Vener AV, Strålfors P. Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes. Clin Epigenetics 2013; 5: 15.
10. Martin-Gronert MS, Ozanne SE. Mechanisms underlying the developmental origins of disease. Rev Endocr Metab Disord 2012; 13: 85-92.
11. Keane E, Layte R, Harrington J, Kearney PM, Perry IJ. Measured parental weight status and familial socio-economic status correlates with childhood overweight and obesity at age 9. PLoS One 2012; 7: e43503.
12. Muhlhausler BS, Gugusheff JR, Ong ZY, Vithayathil M. Nutritional approaches to breaking the intergenerational cycle of obesity. Can J Physiol Pharmacol 2013; 91: 421-428.
13. Lavebratt C, Almgren M, Ekström TJ. Epigenetic regulation in obesity. Int J Obes (Lond) 2012; 36: 757-765.
14. McMillen IC, Rattanatray L, Duffield JA, Morrison JL, MacLaughlin SM, Gentili S et al. The early origins of later obesity: pathways and mechanisms. Adv Exp Med Biol 2009; 646: 71-81.
15. McMillen IC, MacLaughlin SM, Muhlhausler BS, Gentili S, Duffield JL, Morrison JL. Developmental origins of adult health and disease: the role of periconceptional and foetal nutrition. Basic Clin Pharmacol Toxicol 2008; 102: 82-89.
16. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989; 298: 564-567.
17. Schellong K, Schulz S, Harder T, Plagemann A. Birth weight and long-term overweight risk: systematic review and a meta-analysis including 643,902 persons from 66 studies and 26 countries globally. PLoS One 2012; 7: e47776.
18. Whincup PH, Kaye SJ, Owen CG, Huxley R, Cook DG, Anazawa S et al. Birth weight and risk of type 2 diabetes: a systematic review. JAMA 2008; 300: 2886-2897.
19. Gillman MW, Barker D, Bier D, Cagampang F, Challis J, Fall C et al. Meeting report on the 3rd International Congress on Developmental Origins of Health and Disease (DOHaD). Pediatr Res 2007; 61: 625-629.
20. Osmond C, Barker DJ. Fetal, infant, and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women. Environ Health Perspect 2000; 108 : 545-553.
21. Barker DJ, Godfrey K, Gluckman P, Harding J, Owens J, Robinson J. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938-941.
22. Seki Y, Williams L, Vuguin PM, Charron MJ. Minireview: epigenetic programming of diabetes and obesity: animal models. Endocrinology 2012; 153: 1031-1038.
23. Ainge H, Thompson C, Ozanne SE, Rooney KB. A systematic review on animal models of maternal high fat feeding and offspring glycaemic control. Int J Obes (Lond) 2011; 35: 325-335.
24. Zhang S, Rattanatray L, MacLaughlin SM, Cropley JE, Suter CM, Molloy L et al. Periconceptional undernutrition in normal and overweight ewes leads to increased adrenal growth and epigenetic changes in adrenal IGF2/H19 gene in offspring. FASEB J 2010; 24: 2772-2782.
25. Nicholas LM, Rattanatray L, Maclaughlin SM, Ozanne SE, Kleemann DO, Walker SK et al. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring. FASEB J 2013; 27: 3786-3796.
26. Tobi EW, Slagboom PE, van Dongen J, Kremer D, Stein AD, Putter H et al. Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19. PLoS One 2012; 7: e37933.
27. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 2008; 105: 17046-17049.
28. Stein AD, Kahn HS, Rundle A, Zybert PA, van der Pal-de Bruin K, Lumey LH. Anthropometric measures in middle age after exposure to famine during gestation: evidence from the Dutch famine. Am J Clin Nutr 2007; 85: 869-876.
29. Ravelli A, van der Meulen J, Michels R, Osmond C, Barker D, Hales C et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet 1998; 351: 173-177.
30. Lumey LH, Stein AD, Kahn HS, Romijn JA. Lipid profiles in middle-aged men and women after famine exposure during gestation: the Dutch Hunger Winter Families Study. Am J Clin Nutr 2009; 89: 1737-1743.
31. Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochim Biophys Acta 2007; 1775: 138-162.
32. Piyathilake CJ, Badiga S, Alvarez RD, Partridge EE, Johanning GL. A lower degree of PBMC L1 methylation is associated with excess body weight and higher HOMA-IR in the presence of lower concentrations of plasma folate. PLoS One 2013; 8: e54544.
33. Zhang FF, Cardarelli R, Carroll J, Fulda KG, Kaur M, Gonzalez K et al. Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood. Epigenetics 2011; 6: 623-629.
34. Zhu Z-Z, Hou L, Bollati V, Tarantini L, Marinelli B, Cantone L et al. Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemiol 2012; 41: 126-139.
35. Gomes MVM, Toffoli L V, Arruda DW, Soldera LM, Pelosi GG, Neves-Souza RD et al. Age-related changes in the global DNA methylation profile of leukocytes are linked to nutrition but are not associated with the MTHFR C677T genotype or to functional capacities. PLoS One 2012; 7: e52570.
36. Pearce MS, McConnell JC, Potter C, Barrett LM, Parker L, Mathers JC et al. Global LINE-1 DNA methylation is associated with blood glycaemic and lipid profiles. Int J Epidemiol 2012; 41: 210-217.
37. Zhang F, Santella R, Wolff M. White blood cell global methylation and IL-6 promoter methylation in association with diet and lifestyle risk factors in a cancer-free population. Epigenetics 2012; 7: 606-614.
38. Ulrich CM, Toriola AT, Koepl LM, Sandifer T, Poole EM, Duggan C et al. Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women. Epigenetics 2012; 7: 1020-1028.
39. Figueiredo JC, Grau MV, Wallace K, Levine AJ, Shen L, Hamdan R et al. Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors. Cancer Epidemiol Biomarkers Prev 2009; 18: 1041-1049.
40. Nomura Y, Lambertini L, Rialdi A, Lee M, Mystal EY, Grabie M et al. Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity. Reprod Sci 2013; 21: 131-137.
41. Jintaridth P, Tungtrongchitr R, Preutthipan S, Mutirangura A. Hypomethylation of alu elements in post-menopausal women with osteoporosis. PLoS One 2013; 8: e70386.
42. Cash HL, McGarvey ST, Houseman EA, Marsit CJ, Hawley NL, Lambert-Messerlian GM et al. Cardiovascular disease risk factors and DNA methylation at the LINE-1 repeat region in peripheral blood from Samoan Islanders. Epigenetics 2011; 6: 1257-1264.
43. Kim M, Long TI, Arakawa K, Wang R, Yu MC, Laird PW. DNA methylation as a biomarker for cardiovascular disease risk. PLoS One 2010; 5: e9692.
44. Perng W, Rozek LS, Mora-Plazas M, Duchin O, Marin C, Forero Y et al. Micronutrient status and global DNA methylation in school-age children. Epigenetics 2012; 7: 1133-1141.
45. Perng W, Mora-Plazas M, Marín C, Rozek LS, Baylin A, Villamor E. A prospective study of LINE-1 DNA methylation and development of adiposity in school-age Children. PLoS One 2013; 8: e62587.
46. El-Maarri O, Becker T, Junen J, Manzoor SS, Diaz-Lacava A, Schwaab R et al. Gender specific differences in levels of DNA methylation at selected loci from human total blood: a tendency toward higher methylation levels in males. Hum Genet 2007; 122: 505-514.
47. Subramanyam MA, Diez-Roux AV, Pilsner JR, Villamor E, Donohue KM, Liu Y et al. Social factors and leukocyte DNA methylation of repetitive sequences: the multiethnic study of atherosclerosis. PLoS One 2013; 8: e54018.
48. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 2011; 13: 97-109.
49. Park LK, Friso S, Choi S-W. Nutritional influences on epigenetics and age-related disease. Proc Nutr Soc 2012; 71: 75-83.
50. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012; 13: 484-492.
51. Hermsdorff HH, Mansego ML, Campión J, Milagro FI, Zulet MA, Martínez JA. TNFalpha promoter methylation in peripheral white blood cells: Relationship with circulating TNFα, truncal fat and n-6 PUFA intake in young women. Cytokine 2013; 64: 265-271.
52. Barres R, Kirchner H, Rasmussen M, Yan J, Kantor FR, Krook A et al. Weight loss after gastric bypass surgery in human obesity remodels promoter methylation. Cell Rep 2013; 3: 1020-1027.
53. Obermann-Borst SA, Eilers PHC, Tobi EW, de Jong FH, Slagboom PE, Heijmans BT et al. Duration of breastfeeding and gender are associated with methylation of the LEPTIN gene in very young children. Pediatr Res 2013; 74: 344-349.
54. Kuehnen P, Mischke M, Wiegand S, Sers C, Horsthemke B, Lau S et al. An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. PLoS Genet 2012; 8: e1002543.
55. Milagro FI, Gómez-Abellán P, Campión J, Martínez JA, Ordovás JM, Garaulet M. CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake. Chronobiol Int 2012; 29: 1180-1194.
56. Stepanow S, Reichwald K, Huse K, Gausmann U, Nebel A, Rosenstiel P et al. Allele-specific, age-dependent and BMI-associated DNA methylation of human MCHR1. PLoS One 2011; 6: e17711.
57. Zhao J, Goldberg J, Vaccarino V. Promoter methylation of serotonin transporter gene is associated with obesity measures: a monozygotic twin study. Int J Obes (Lond) 2013; 37: 140-145.
58. Movérare-Skrtic S, Mellström D, Vandenput L, Ehrich M, Ohlsson C. Peripheral blood leukocyte distribution and body mass index are associated with the methylation pattern of the androgen receptor promoter. Endocrine 2009; 35: 204-210.
59. Drake AJ, McPherson RC, Godfrey KM, Cooper C, Lillycrop K, Hanson M et al. An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and foetal growth. Clin Endocrinol (Oxf) 2012; 77: 808-815.
60. Huang R-C, Galati JC, Burrows S, Beilin LJ, Li X, Pennell CE et al. DNA methylation of the IGF2/H19 imprinting control region and adiposity distribution in young adults. Clin Epigenetics 2012; 4: 21.
61. Almén MS, Jacobsson J, Moschonis G, Benedict C, Chrousos GP, Fredriksson R et al. Genome wide analysis reveals association of a FTO gene variant with epigenetic changes. Genomics 2012; 99: 132-137.
62. Xu X, Su S, Barnes V, De Miguel C, Pollock J, Ownby D et al. A genome-wide methylation study on obesity: differential variability and differential methylation. Epigenetics 2013; 8: 522-533.
63. Wang X, Zhu H, Snieder H, Su S, Munn D, Harshfield G et al. Obesity related methylation changes in DNA of peripheral blood leukocytes. BMC Med 2010; 8: 87.
64. Feinberg AP, Irizarry R, Fradin D, Aryee MJ, Murakami P, Aspelund T et al. Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci Transl Med 2010; 2: 49-67.
65. Rönn T, Volkov P, Davegårdh C, Dayeh T, Hall E, Olsson AH et al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 2013; 9: e1003572.
66. Milagro FI, Campión J, Cordero P, Goyenechea E, Gómez-Uriz AM, Abete I et al. A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss. FASEB J 2011; 25: 1378-1389.
67. Moleres A, Campión J, Milagro FI, Marcos A, Campoy C, Garagorri JM et al. Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study. FASEB J 2013; 27: 2504-2512.
68. Bouchard L, Rabasa-Lhoret R, Faraj M, Lavoie M, Mill J, Pérusse L et al. Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction. Am J Clin Nutr 2010; 91: 309-321.
69. Cordero P, Campion J, Milagro FI, Goyenechea E, Steemburgo T, Javierre BM et al. Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet. J Physiol Biochem 2011; 67: 463-470.
70. Reynolds RM, Jacobsen GH, Drake AJ. What is the evidence in humans that DNA methylation changes link events in utero and later life disease? Clin Endocrinol (Oxf) 2013; 78: 814-822.
71. Lam LL, Emberly E, Fraser HB, Neumann SM, Chen E, Miller GE et al. Factors underlying variable DNA methylation in a human community cohort. Proc Natl Acad Sci USA 2012; 109 : 17253-17260.
72. Joubert BR, Håberg SE, Nilsen RM, Wang X, Vollset SE, Murphy SK et al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect 2012; 120: 1425-1431.
73. Soubry A, Schildkraut JM, Murtha A, Wang F, Huang Z, Bernal A et al. Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med 2013; 11: 29.
74. Michels KB, Harris HR, Barault L. Birthweight, maternal weight trajectories and global DNA methylation of LINE-1 repetitive elements. PLoS One 2011; 6: e25254.
75. St-Pierre J, Hivert M-F, Perron P, Poirier P, Guay S-P, Brisson D et al. IGF2 DNA methylation is a modulator of newborn's fetal growth and development. Epigenetics 2012; 7: 1125-1132.
76. Guenard F, Deshaies Y, Cianflone K, Kral JG, Marceau P, Vohl M-C. Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery. Proc Natl Acad Sci USA 2013; 110: 11439-11444.
77. Guénard F, Tchernof A, Deshaies Y, Cianflone K, Kral JG, Marceau P et al. Methylation and expression of immune and inflammatory genes in the offspring of bariatric bypass surgery patients. J Obes 2013; 2013: 492170.
78. Perkins E, Murphy SK, Murtha AP, Schildkraut J, Jirtle RL, Demark-Wahnefried W et al. Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children. J Pediatr 2012; 161: 31-39.
79. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop K, Burdge GC, McLean C et al. Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes 2011; 60: 1528-1534.
80. Relton CL, Groom ASt, Pourcain B, Sayers AE, Swan DC, Embleton ND et al. DNA methylation patterns in cord blood DNA and body size in childhood. PLoS One 2012; 7: e31821.
81. Groom A, Potter C, Swan DC, Fatemifar G, Evans DM, Ring SM et al. Postnatal growth and DNA methylation are associated with differential gene expression of the TACSTD2 gene and childhood fat mass. Diabetes 2012; 61: 391-400.
82. Söhle J, Machuy N, Smailbegovic E, Holtzmann U, Grönniger E, Wenck H et al. Identification of new genes involved in human adipogenesis and fat storage. PLoS One 2012; 7: e31193.
83. Issa J-P, Just W, Sugii S, Evans RM. Epigenetic codes of PPARγ in metabolic disease. FEBS Lett 2011; 585: 2121-2128.
84. Ribel-Madsen R, Fraga MF, Jacobsen S, Bork-Jensen J, Lara E, Calvanese V et al. Genome-wide analysis of DNA methylation differences in muscle and fat from monozygotic twins discordant for type 2 diabetes. PLoS One 2012; 7: e51302.
85. Ling C, Del Guerra S, Lupi R, Rönn T, Granhall C, Luthman H et al. Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia 2008; 51: 615-622.
86. Cooper WN, Khulan B, Owens S, Elks CE, Seidel V, Prentice AM et al. DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. FASEB J 2012; 26: 1782-1790.
87. Sferruzzi-Perri AN, Vaughan OR, Haro M, Cooper WN, Musial B, Charalambous M et al. An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory. FASEB J 2013; 27: 3928-3937.
88. Głowińska-Olszewska B, Urban M. Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in obese children and adolescents. Metabolism 2007; 56: 799-805.
89. Jaffe AE, Feinberg AP, Irizarry R, Leek JT. Significance analysis and statistical dissection of variably methylated regions. Biostatistics 2012; 13: 166-178.
90. Feinberg AP, Irizarry RA. Evolution in health and medicine Sackler colloquium: stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease. Proc Natl Acad Sci USA 2010; 107 : 1757-1764.
91. Ge K. Epigenetic regulation of adipogenesis by histone methylation. Biochim Biophys Acta 2012; 1819: 727-732.
92. Reinius LE, Acevedo N, Joerink M, Pershagen G, Dahlén S-E, Greco D et al. Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility. PLoS One 2012; 7: e41361.
93. Wu H-C, Delgado-Cruzata L, Flom JD, Kappil M, Ferris JS, Liao Y et al. Global methylation profiles in DNA from different blood cell types. Epigenetics 2011; 6: 76-85.
94. Jacoby M, Gohrbandt S, Clausse V, Brons NH, Muller CP. Interindividual variability and co-regulation of DNA methylation differ among blood cell populations. Epigenetics 2012; 7: 1421-1434.
95. Adalsteinsson BT, Gudnason H, Aspelund T, Harris TB, Launer LJ, Eiriksdottir G et al. Heterogeneity in white blood cells has potential to confound DNA methylation measurements. PLoS One 2012; 7: e46705.
96. Talens RP, Boomsma DI, Tobi EW, Kremer D, Jukema JW, Willemsen G, Putter H, Slagboom PE, Heijmans BT et al. Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J 2010; 24: 3135-3144.
97. Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA 2008; 299: 2877-2883.
98. Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol 2013; 31: 142-147.
99. Koestler DC, Christensen B, Karagas MR, Marsit CJ, Langevin SM, Kelsey KT et al. Blood-based profiles of DNA methylation predict the underlying distribution of cell types: A validation analysis. Epigenetics 2013; 8: 816-826.
100. Ziller MJ, Gu H, Müller F, Donaghey J, Tsai LT-Y, Kohlbacher O et al. Charting a dynamic DNA methylation landscape of the human genome. Nature 2013; 500: 477-481.
101. Tam CS, Lecoultre V, Ravussin E. Brown adipose tissue: mechanisms and potential therapeutic targets. Circulation 2012; 125: 2782-2791.
102. Hollegaard MV, Grauholm J, Nørgaard-Pedersen B, Hougaard DM. DNA methylome profiling using neonatal dried blood spot samples: a proof-ofprinciple study. Mol Genet Metab 2013; 108: 225-231.
103. Wong N, Morley R, Saffery R, Craig J. Archived Guthrie blood spots as a novel source for quantitative DNA methylation analysis. Biotechniques 2008; 45: 423-428.
104. Heyn H, Moran S, Hernando-Herraez I, Sayols S, Gomez A, Sandoval J et al. DNA methylation contributes to natural human variation. Genome Res 2013; 23: 1363-1372.
105. Wang D, Liu X, Zhou Y, Xie H, Hong X, Tsai H-J et al. Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life. Epigenetics 2012; 7: 594-605.
106. Alisch RS, Barwick BG, Chopra P, Myrick LK, Satten G, Conneely KN et al. Age-associated DNA methylation in pediatric populations. Genome Res 2012; 22: 623-632.
107. Byun HM, Nordio F, Coull B, Tarantini L, Hou L, Bonzini M et al. Temporal stability of epigenetic markers: sequence characteristics and predictors of short-term DNA methylation variations. PLoS One 2012; 7: e39220.
108. Murphy SK, Huang Z, Hoyo C. Differentially methylated regions of imprinted genes in prenatal, perinatal and postnatal human tissues. PLoS One 2012; 7: e40924.
109. Bock C, Walter J, Paulsen M, Lengauer T. Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping. Nucleic Acids Res 2008; 36: e55.
110. Gordon L, Joo JE, Powell JE, Ollikainen M, Novakovic B, Li X et al. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence. Genome Res 2012; 22: 1395-1406.
111. Drong AW, Nicholson G, Hedman AK, Meduri E, Grundberg E, Small KS et al. The presence of methylation quantitative trait Loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue. PLoS One 2013; 8: e55923.
112. Dayeh TA, Olsson AH, Volkov P, Almgren P, Rönn T, Ling C. Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets. Diabetologia 2013; 56: 1036-1046.
113. Meaburn EL, Schalkwyk LC, Mill J. Allele-specific methylation in the human genome: implications for genetic studies of complex disease. Epigenetics 2010; 5: 578-582.
114. 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 2012; 41: 161-176.
115. ARIES-Accessible Resource for Integrated Epigenomics Studies. Available from: http://www.ariesepigenomics.org.uk/.
116. MuTHER-Multiple Tissue Human Expression Resource. Available from: http://www.muther.ac.uk/.
117. EpiTwin Website. Available from: http://www.epitwin.eu/index.html.
118. Saffery R, Morley R, Carlin JB, Joo J-HE, Ollikainen M, Novakovic B et al. Cohort profile: the peri/post-natal epigenetic twins study. Int J Epidemiol 2012; 41: 55-61.
119. Petersen A-K, Zeilinger S, Kastenmüller G, Römisch-Margl W, Brugger M, Peters A et al. Epigenetics meets metabolomics: an epigenome-wide association study with blood serum metabolic traits. Hum Mol Genet 2013; 23: 534-545.
120. Makrides M, Gibson RA, Mcphee AJ, Yelland L, Quinlivan J, Ryan P. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA 2010; 304: 1675-1683.
121. Souren NYP, Tierling S, Fryns J-P, Derom C, Walter J, Zeegers MP. DNA methylation variability at growth-related imprints does not contribute to overweight in monozygotic twins discordant for BMI. Obesity (Silver Spring) 2011; 19: 1519-1522.
122. Carless MA, Kulkarni H, Kos MZ, Charlesworth J, Peralta JM, Göring HHH et al. Genetic effects on DNA methylation and its potential relevance for obesity in mexican americans. PLoS One 2013; 8: e73950.
123. Marchi M, Lisi S, Curcio M, Barbuti S, Piaggi P, Ceccarini G et al. Human leptin tissue distribution, but not weight loss-dependent change in expression, is associated with methylation of its promoter. Epigenetics 2011; 6: 1198-1206.