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

Florianne Vehmeijer 1 Leanne Küpers 2, 3 Gemma Sharp 2 Lucas Salas 4, 5, 6, 7 Samantha Lent 8 Dereje Jima 9 Gwen Tindula 10 Sarah Reese 11 Cancan Qi 12, 13 Olena Gruzieva 14, 15 Christian Page 16, 17 Faisal Rezwan 18, 19 Philip Melton 20, 21 Ellen Nohr 22, 23 Geòrgia Escaramís 7, 24, 25 Peter Rzehak 26 Anni Heiskala 27 Tong Gong 14 Samuli Tuominen 28 Lu Gao 29 Jason Ross 30 Anne Starling 31, 32 John Holloway 19 Paul Yousefi 2 Gunn Marit Aasvang 16 Lawrence Beilin 21 Anna Bergström 14, 15 Elisabeth Binder 33, 34 Leda Chatzi 35 Eva Corpeleijn 3, 12 Darina Czamara 33 Brenda Eskenazi 10 Susan Ewart 36 Natalia Ferre 37 Veit Grote 26 Dariusz Gruszfeld 38 Siri Håberg 16 Cathrine Hoyo 9 Karen Huen 10 Robert Karlsson 14 Inger Kull 14, 39 Jean-Paul Langhendries 40 Johanna Lepeule 41, 42 Maria Magnus 2, 16 Rachel Maguire 9, 43 Peter Molloy 30 Claire Monnereau 1 Trevor Mori 21 Emily Oken 44 Katri Räikkönen 28 Sheryl Rifas-Shiman 44 Carlos Ruiz-Arenas 5, 6, 7 Sylvain Sebert 27 Vilhelmina Ullemar 14 Elvira Verduci 45 Judith Vonk 3, 12 Cheng-Jian Xu 3, 12, 46, 47 Ivana Yang 31, 48, 49 Hongmei Zhang 50 Weiming Zhang 31 Wilfried Karmaus 50 Dana Dabelea 31, 32 Beverly Muhlhausler 51 Carrie Breton 29 Jari Lahti 28, 52 Catarina Almqvist 14, 53 Marjo-Riitta Jarvelin 27, 54, 55, 56 Berthold Koletzko 26 Martine Vrijheid 5, 6, 7 Thorkild Sørensen 2, 57 Rae-Chi Huang 21 Syed Hasan Arshad 19, 58 Wenche Nystad 16 Erik Melén 14, 39 Gerard Koppelman 59, 12 Stephanie London 11 Nina Holland 10 Mariona Bustamante 5, 6, 7 Susan Murphy 43 Marie-France Hivert 44, 60, 61 Andrea Baccarelli 62 Caroline Relton 2 Harold Snieder 12, 3 Vincent Jaddoe 1 Janine Felix 1
Abstract : 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 < 1.06 × 10−7, 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.
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Florianne Vehmeijer, Leanne Küpers, Gemma Sharp, Lucas Salas, Samantha Lent, et al.. DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies. Genome Medicine, BioMed Central, 2020, 12 (1), pp.105. ⟨10.1186/s13073-020-00810-w⟩. ⟨inserm-03179265⟩

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