DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies
Authors: Vehmeijer Florianne O. L. , Küpers Leanne K. , Sharp Gemma C. , Salas Lucas A. , Lent Samantha , Jima Dereje D. , Tindula Gwen , Reese Sarah , Qi Cancan , Gruzieva Olena , Page Christian , Rezwan Faisal I. , Melton Philip E. , Nohr Ellen , Escaramís Geòrgia , Rzehak Peter , Heiskala Anni , Gong Tong , Tuominen Samuli T. , Gao Lu , Ross Jason P. , Starling Anne P. , Holloway John W. , Yousefi Paul , Aasvang Gunn Marit , Beilin Lawrence J. , Bergström Anna , Binder Elisabeth , Chatzi Leda , Corpeleijn Eva , Czamara Darina , Eskenazi Brenda , Ewart Susan , Ferre Natalia , Grote Veit , Gruszfeld Dariusz , Håberg Siri E. , Hoyo Cathrine , Huen Karen , Karlsson Robert , Kull Inger , Langhendries Jean-Paul , Lepeule Johanna , Magnus Maria C. , Maguire Rachel L. , Molloy Peter L. , Monnereau Claire , Mori Trevor A. , Oken Emily , Räikkönen Katri , Rifas-Shiman Sheryl , Ruiz-Arenas Carlos , Sebert Sylvain , Ullemar Vilhelmina , Verduci Elvira , Vonk Judith M. , Xu Cheng-jian , Yang Ivana V. , Zhang Hongmei , Zhang Weiming , Karmaus Wilfried , Dabelea Dana , Muhlhausler Beverly S. , Breton Carrie V. , Lahti Jari , Almqvist Catarina , Jarvelin Marjo-Riitta , Koletzko Berthold , Vrijheid Martine , Sørensen Thorkild I. A. , Huang Rae-Chi , Arshad Syed Hasan , Nystad Wenche , Melén Erik , Koppelman Gerard H. , London Stephanie J. , Holland Nina , Bustamante Mariona , Murphy Susan K. , Hivert Marie-France , Baccarelli Andrea , Relton Caroline L. , Snieder Harold , Jaddoe Vincent W. V. , Felix Janine F. 
Published: November 2020

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 (birthPenrichment = 1; childhoodPenrichment = 2.00 × 10−4; adolescencePenrichment = 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.