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

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

In: Genome Medicine, Vol. 12, No. 1, 105, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Vehmeijer, FOL, Küpers, LK, Sharp, GC, Salas, LA, Lent, S, Jima, DD, Tindula, G, Reese, S, Qi, C, Gruzieva, O, Page, C, Rezwan, FI, Melton, PE, Nohr, E, Escaramís, G, Rzehak, P, Heiskala, A, Gong, T, Tuominen, ST, Gao, L, Ross, JP, Starling, AP, Holloway, JW, Yousefi, P, Aasvang, GM, Beilin, LJ, Bergström, A, Binder, E, Chatzi, L, Corpeleijn, E, Czamara, D, Eskenazi, B, Ewart, S, Ferre, N, Grote, V, Gruszfeld, D, Håberg, SE, Hoyo, C, Huen, K, Karlsson, R, Kull, I, Langhendries, JP, Lepeule, J, Magnus, MC, Maguire, RL, Molloy, PL, Monnereau, C, Mori, TA, Oken, E, Räikkönen, K, Rifas-Shiman, S, Ruiz-Arenas, C, Sebert, S, Ullemar, V, Verduci, E, Vonk, JM, Xu, CJ, Yang, IV, Zhang, H, Zhang, W, Karmaus, W, Dabelea, D, Muhlhausler, BS, Breton, CV, Lahti, J, Almqvist, C, Jarvelin, MR, Koletzko, B, Vrijheid, M, Sørensen, TIA, Huang, RC, Arshad, SH, Nystad, W, Melén, E, Koppelman, GH, London, SJ, Holland, N, Bustamante, M, Murphy, SK, Hivert, MF, Baccarelli, A, Relton, CL, Snieder, H, Jaddoe, VWV & Felix, JF 2020, 'DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies', Genome Medicine, vol. 12, no. 1, 105. https://doi.org/10.1186/s13073-020-00810-w

APA

Vehmeijer, F. O. L., Küpers, L. K., Sharp, G. C., Salas, L. A., Lent, S., Jima, D. D., Tindula, G., Reese, S., Qi, C., Gruzieva, O., Page, C., Rezwan, F. I., Melton, P. E., Nohr, E., Escaramís, G., Rzehak, P., Heiskala, A., Gong, T., Tuominen, S. T., ... Felix, J. F. (2020). DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies. Genome Medicine, 12(1), [105]. https://doi.org/10.1186/s13073-020-00810-w

Vancouver

Vehmeijer FOL, Küpers LK, Sharp GC, Salas LA, Lent S, Jima DD et al. DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies. Genome Medicine. 2020;12(1). 105. https://doi.org/10.1186/s13073-020-00810-w

Author

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. / DNA methylation and body mass index from birth to adolescence : meta-analyses of epigenome-wide association studies. In: Genome Medicine. 2020 ; Vol. 12, No. 1.

Bibtex

@article{5d9c9aaa90ff48428658f776c816b494,
title = "DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies",
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.",
keywords = "Body mass index, Childhood obesity, DNA methylation, Epigenetics",
author = "Vehmeijer, {Florianne O.L.} and K{\"u}pers, {Leanne K.} and Sharp, {Gemma C.} and Salas, {Lucas A.} and Samantha Lent and Jima, {Dereje D.} and Gwen Tindula and Sarah Reese and Cancan Qi and Olena Gruzieva and Christian Page and Rezwan, {Faisal I.} and Melton, {Philip E.} and Ellen Nohr and Ge{\`o}rgia Escaram{\'i}s and Peter Rzehak and Anni Heiskala and Tong Gong and Tuominen, {Samuli T.} and Lu Gao and Ross, {Jason P.} and Starling, {Anne P.} and Holloway, {John W.} and Paul Yousefi and Aasvang, {Gunn Marit} and Beilin, {Lawrence J.} and Anna Bergstr{\"o}m and Elisabeth Binder and Leda Chatzi and Eva Corpeleijn and Darina Czamara and Brenda Eskenazi and Susan Ewart and Natalia Ferre and Veit Grote and Dariusz Gruszfeld and H{\aa}berg, {Siri E.} and Cathrine Hoyo and Karen Huen and Robert Karlsson and Inger Kull and Langhendries, {Jean Paul} and Johanna Lepeule and Magnus, {Maria C.} and Maguire, {Rachel L.} and Molloy, {Peter L.} and Claire Monnereau and Mori, {Trevor A.} and Emily Oken and Katri R{\"a}ikk{\"o}nen and Sheryl Rifas-Shiman and Carlos Ruiz-Arenas and Sylvain Sebert and Vilhelmina Ullemar and Elvira Verduci and Vonk, {Judith M.} and Xu, {Cheng jian} and Yang, {Ivana V.} and Hongmei Zhang and Weiming Zhang and Wilfried Karmaus and Dana Dabelea and Muhlhausler, {Beverly S.} and Breton, {Carrie V.} and Jari Lahti and Catarina Almqvist and Jarvelin, {Marjo Riitta} and Berthold Koletzko and Martine Vrijheid and S{\o}rensen, {Thorkild I.A.} and Huang, {Rae Chi} and Arshad, {Syed Hasan} and Wenche Nystad and Erik Mel{\'e}n and Koppelman, {Gerard H.} and London, {Stephanie J.} and Nina Holland and Mariona Bustamante and Murphy, {Susan K.} and Hivert, {Marie France} and Andrea Baccarelli and Relton, {Caroline L.} and Harold Snieder and Jaddoe, {Vincent W.V.} and Felix, {Janine F.}",
year = "2020",
doi = "10.1186/s13073-020-00810-w",
language = "English",
volume = "12",
journal = "Genome Medicine",
issn = "1756-994X",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - DNA methylation and body mass index from birth to adolescence

T2 - meta-analyses of epigenome-wide association studies

AU - Vehmeijer, Florianne O.L.

AU - Küpers, Leanne K.

AU - Sharp, Gemma C.

AU - Salas, Lucas A.

AU - Lent, Samantha

AU - Jima, Dereje D.

AU - Tindula, Gwen

AU - Reese, Sarah

AU - Qi, Cancan

AU - Gruzieva, Olena

AU - Page, Christian

AU - Rezwan, Faisal I.

AU - Melton, Philip E.

AU - Nohr, Ellen

AU - Escaramís, Geòrgia

AU - Rzehak, Peter

AU - Heiskala, Anni

AU - Gong, Tong

AU - Tuominen, Samuli T.

AU - Gao, Lu

AU - Ross, Jason P.

AU - Starling, Anne P.

AU - Holloway, John W.

AU - Yousefi, Paul

AU - Aasvang, Gunn Marit

AU - Beilin, Lawrence J.

AU - Bergström, Anna

AU - Binder, Elisabeth

AU - Chatzi, Leda

AU - Corpeleijn, Eva

AU - Czamara, Darina

AU - Eskenazi, Brenda

AU - Ewart, Susan

AU - Ferre, Natalia

AU - Grote, Veit

AU - Gruszfeld, Dariusz

AU - Håberg, Siri E.

AU - Hoyo, Cathrine

AU - Huen, Karen

AU - Karlsson, Robert

AU - Kull, Inger

AU - Langhendries, Jean Paul

AU - Lepeule, Johanna

AU - Magnus, Maria C.

AU - Maguire, Rachel L.

AU - Molloy, Peter L.

AU - Monnereau, Claire

AU - Mori, Trevor A.

AU - Oken, Emily

AU - Räikkönen, Katri

AU - Rifas-Shiman, Sheryl

AU - Ruiz-Arenas, Carlos

AU - Sebert, Sylvain

AU - Ullemar, Vilhelmina

AU - Verduci, Elvira

AU - Vonk, Judith M.

AU - Xu, Cheng jian

AU - Yang, Ivana V.

AU - Zhang, Hongmei

AU - Zhang, Weiming

AU - Karmaus, Wilfried

AU - Dabelea, Dana

AU - Muhlhausler, Beverly S.

AU - Breton, Carrie V.

AU - Lahti, Jari

AU - Almqvist, Catarina

AU - Jarvelin, Marjo Riitta

AU - Koletzko, Berthold

AU - Vrijheid, Martine

AU - Sørensen, Thorkild I.A.

AU - Huang, Rae Chi

AU - Arshad, Syed Hasan

AU - Nystad, Wenche

AU - Melén, Erik

AU - Koppelman, Gerard H.

AU - London, Stephanie J.

AU - Holland, Nina

AU - Bustamante, Mariona

AU - Murphy, Susan K.

AU - Hivert, Marie France

AU - Baccarelli, Andrea

AU - Relton, Caroline L.

AU - Snieder, Harold

AU - Jaddoe, Vincent W.V.

AU - Felix, Janine F.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Body mass index

KW - Childhood obesity

KW - DNA methylation

KW - Epigenetics

U2 - 10.1186/s13073-020-00810-w

DO - 10.1186/s13073-020-00810-w

M3 - Journal article

C2 - 33239103

AN - SCOPUS:85096588131

VL - 12

JO - Genome Medicine

JF - Genome Medicine

SN - 1756-994X

IS - 1

M1 - 105

ER -

ID: 253275614