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

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

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 P enrichment = 1; childhood P enrichment = 2.00 × 10 −4; adolescence P enrichment = 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.

Body mass index, Childhood obesity, DNA methylation, Epigenetics
1756-994X
Vehmeijer, Florianne O. L.
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Küpers, Leanne K.
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Sharp, Gemma C.
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Salas, Lucas A.
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Lent, Samantha
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Jima, Dereje D.
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Tindula, Gwen
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Page, Christian
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Rezwan, Faisal I.
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Küpers, Leanne K.
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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. and Felix, Janine F. (2020) DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies. Genome Medicine, 12 (1), [105]. (doi:10.1186/s13073-020-00810-w).

Record type: Article

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 P enrichment = 1; childhood P enrichment = 2.00 × 10 −4; adolescence P enrichment = 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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Accepted/In Press date: 12 November 2020
Published date: 25 December 2020
Keywords: Body mass index, Childhood obesity, DNA methylation, Epigenetics

Identifiers

Local EPrints ID: 445915
URI: http://eprints.soton.ac.uk/id/eprint/445915
ISSN: 1756-994X
PURE UUID: 2f0c3cd3-ae17-406e-881a-89c9ac48a802
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 13 Jan 2021 17:31
Last modified: 26 Nov 2021 03:00

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Contributors

Author: Florianne O. L. Vehmeijer
Author: Leanne K. Küpers
Author: Gemma C. Sharp
Author: Lucas A. Salas
Author: Samantha Lent
Author: Dereje D. Jima
Author: Gwen Tindula
Author: Sarah Reese
Author: Cancan Qi
Author: Olena Gruzieva
Author: Christian Page
Author: Faisal I. Rezwan ORCID iD
Author: Philip E. Melton
Author: Ellen Nohr
Author: Geòrgia Escaramís
Author: Peter Rzehak
Author: Anni Heiskala
Author: Tong Gong
Author: Samuli T. Tuominen
Author: Lu Gao
Author: Jason P. Ross
Author: Anne P. Starling
Author: Paul Yousefi
Author: Gunn Marit Aasvang
Author: Lawrence J. Beilin
Author: Anna Bergström
Author: Elisabeth Binder
Author: Leda Chatzi
Author: Eva Corpeleijn
Author: Darina Czamara
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