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DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies


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Vehmeijer, FOL, Kupers, LK, Sharp, GC, Salas, LA, Lent, S, Jima, DD, Tindula, G, Reese, S, Qi, C, Gruzieva, O, Page, C, Rezwan, FI, Melton, PE ORCID: 0000-0003-4026-2964, Nohr, E, Escaramis, G, Rzehak, P, Heiskala, A, Gong, T, Tuominen, ST, Gao, L, Ross, JP, Starling, AP, Holloway, JW, Yousefi, P, Aasvang, GM, Beilin, LJ, Bergstrom, A, Binder, E, Chatzi, L, Corpeleijn, E, Czamara, D, Eskenazi, B, Ewart, S, Ferre, N, Grote, V, Gruszfeld, D, Haberg, SE, Hoyo, C, Huen, K, Karlsson, R, Kull, I, Langhendries, J-P, Lepeule, J, Magnus, MC, Maguire, RL, Molloy, PL, Monnereau, C, Mori, TA, Oken, E, Raikkonen, K, Rifas-Shiman, S, Ruiz-Arenas, C, Sebert, S, Ullemar, V, Verduci, E, Vonk, JM, Xu, C-J, Yang, IV, Zhang, H, Zhang, W, Karmaus, W, Dabelea, D, Muhlhausler, BS, Breton, CV, Lahti, J, Almqvist, C, Jarvelin, M-R, Koletzko, B, Vrijheid, M, Sorensen, TIA, Huang, R-C, Arshad, SH, Nystad, W, Melen, E, Koppelman, GH, London, SJ, Holland, N, Bustamante, M, Murphy, SK, Hivert, M-F, Baccarelli, A, Relton, CL, Snieder, H, Jaddoe, VWV and Felix, JF 2020 , 'DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies' , Genome Medicine, vol. 12 , pp. 1-15 , doi: 10.1186/s13073-020-00810-w.

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Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P -7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7).Conclusions: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

Item Type: Article
Authors/Creators:Vehmeijer, FOL and Kupers, LK and Sharp, GC and Salas, LA and Lent, S and Jima, DD and Tindula, G and Reese, S and Qi, C and Gruzieva, O and Page, C and Rezwan, FI and Melton, PE and Nohr, E and Escaramis, G and Rzehak, P and Heiskala, A and Gong, T and Tuominen, ST and Gao, L and Ross, JP and Starling, AP and Holloway, JW and Yousefi, P and Aasvang, GM and Beilin, LJ and Bergstrom, A and Binder, E and Chatzi, L and Corpeleijn, E and Czamara, D and Eskenazi, B and Ewart, S and Ferre, N and Grote, V and Gruszfeld, D and Haberg, SE and Hoyo, C and Huen, K and Karlsson, R and Kull, I and Langhendries, J-P and Lepeule, J and Magnus, MC and Maguire, RL and Molloy, PL and Monnereau, C and Mori, TA and Oken, E and Raikkonen, K and Rifas-Shiman, S and Ruiz-Arenas, C and Sebert, S and Ullemar, V and Verduci, E and Vonk, JM and Xu, C-J and Yang, IV and Zhang, H and Zhang, W and Karmaus, W and Dabelea, D and Muhlhausler, BS and Breton, CV and Lahti, J and Almqvist, C and Jarvelin, M-R and Koletzko, B and Vrijheid, M and Sorensen, TIA and Huang, R-C and Arshad, SH and Nystad, W and Melen, E and Koppelman, GH and London, SJ and Holland, N and Bustamante, M and Murphy, SK and Hivert, M-F and Baccarelli, A and Relton, CL and Snieder, H and Jaddoe, VWV and Felix, JF
Keywords: body mass index, childhood obesity, DNA methylation, epigenetics
Journal or Publication Title: Genome Medicine
Publisher: BioMed Central
ISSN: 1756-994X
DOI / ID Number: 10.1186/s13073-020-00810-w
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© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License (, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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