University of Oulu

Vehmeijer, F.O.L., Küpers, L.K., Sharp, G.C. et al. DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies. Genome Med 12, 105 (2020).

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

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Author: Vehmeijer, Florianne O. L.1,2,3; Kuepers, Leanne K.4,5,6; Sharp, Gemma C.4;
Salas, Lucas A.7,8,9,10; Lent, Samantha11; Jima, Dereje D.12,13; Tindula, Gwen14; Reese, Sarah15; Qi, Cancan16,17; Gruzieva, Olena18,19; Page, Christian20,21; Rezwan, Faisal, I22,23; Melton, Philip E.24,25; Nohr, Ellen26,27; Escaramis, Georgia10,28,29; Rzehak, Peter30; Heiskala, Anni31; Gong, Tong32; Tuominen, Samuli T.33; Gao, Lu34; Ross, Jason P.35; Starling, Anne P.36,37; Holloway, John W.23,38; Yousefi, Paul4; Aasvang, Gunn Marit39; Beilin, Lawrence J.40; Bergstrom, Anna18,19; Binder, Elisabeth41,42; Chatzi, Leda43; Corpeleijn, Eva6; Czamara, Darina41; Eskenazi, Brenda44; Ewart, Susan45; Ferre, Natalia46; Grote, Veit30; Gruszfeld, Dariusz47; Haberg, Siri E.20; Hoyo, Cathrine13,48; Huen, Karen14; Karlsson, Robert32; Kull, Inger49,50; Langhendries, Jean-Paul51; Lepeule, Johanna52; Magnus, Maria C.4,5,20; Maguire, Rachel L.48,53; Molloy, Peter L.35; Monnereau, Claire1,3; Mori, Trevor A.40; Oken, Emily54; Raikkonen, Katri33; Rifas-Shiman, Sheryl54; Ruiz-Arenas, Carlos8,9,10; Sebert, Sylvain31; Ullemar, Vilhelmina32; Verduci, Elvira55; Vonk, Judith M.6,17; Xu, Cheng-jian16,17,56,57; Yang, Ivana, V36,58,59; Zhang, Hongmei60; Zhang, Weiming61; Karmaus, Wilfried60; Dabelea, Dana36,37,62; Muhlhausler, Beverly S.63; Breton, Carrie, V34; Lahti, Jari33,64; Almqvist, Catarina32,65; Jarvelin, Marjo-Riitta31,66,67,68; Koletzko, Berthold30; Vrijheid, Martine8,9,10; Sorensen, Thorkild I. A.4,69; Huang, Rae-Chi70; Arshad, Syed Hasan38,71; Nystad, Wenche72; Melen, Erik49,50; Koppelman, Gerard H.16,17; London, Stephanie J.15; Holland, Nina14; Bustamante, Mariona8,9,10; Murphy, Susan K.53; Hivert, Marie-France54,73,74; Baccarelli, Andrea75; Relton, Caroline L.4; Snieder, Harold6; Jaddoe, Vincent W. V.1,2,3; Felix, Janine F.1,2
Organizations: 1Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Room Na-2918,POB 2040, NL-3000 CA Rotterdam, Netherlands.
2Univ Med Ctr Rotterdam, Dept Pediat, Erasmus MC, Rotterdam, Netherlands.
3Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
4Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
5Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.
6Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
7Geisel Sch Med Dartmouth, Lebanon, NH USA.
8ISGlobal, Barcelona, Spain.
9Univ Pompeu Fabra UPF, Barcelona, Spain.
10CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.
11Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA.
12North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
13North Carolina State Univ, Ctr Human Hlth & Environm, Raleigh, NC USA.
14Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Childrens Environm Hlth Lab, Berkeley, CA 94720 USA.
15NIEHS, US Dept HHS, Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
16Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Pulmonol & Pediat Allergy, Groningen, Netherlands.
17Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands.
18Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
19Ctr Occupat & Environm Med, Reg Stockholm, Stockholm, Sweden.
20Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway.
21Oslo Univ Hosp, Oslo Ctr Biostat & Epidemiol, Oslo, Norway.
22Cranfield Univ, Sch Water Energy & Environm, Cranfield, Beds, England.
23Univ Southampton, Southampton Gen Hosp, Fac Med, Human Dev & Hlth, Southampton, Hants, England.
24Curtin Univ, Sch Pharm & Biomed Sci, Bentley, WA, Australia.
25Univ Western Australia, Sch Biomed Sci, Crawley, WA, Australia.
26Univ South Eastern Norway, Ctr Womens Family & Child Hlth, Kongsberg, Norway.
27Univ Southern Denmark, Inst Clin Res, Odense, Denmark.
28Univ Barcelona, Fac Med & Hlth Sci, Dept Biomed Sci, Barcelona, Spain.
29Univ Girona, Res Grp Stat Econometr & Hlth GRECS, Girona, Spain.
30Ludwig Maximilians Univ Munchen LMU, Div Metab & Nutr Med, Dr von Hauner Childrens Hosp, Munich, Germany.
31Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland.
32Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
33Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland.
34Univ Southern Calif, Dept Prevent Med, Los Angeles, CA USA.
35CSIRO Hlth & Biosecur, N Ryde, NSW, Australia.
36Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA.
37Univ Colorado, Lifecourse Epidemiol Adipos & Diabet LEAD Ctr, Anschutz Med Campus, Aurora, CO USA.
38Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England.
39Norwegian Inst Publ Hlth, Dept Air Pollut & Noise, Oslo, Norway.
40Univ Western Australia, Med Sch, Perth, WA, Australia.
41Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.
42Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA.
43Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
44Univ Calif Berkeley, Sch Publ Hlth, Ctr Environm Res & Childrens Hlth, Berkeley, CA 94720 USA.
45Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA.
46Univ Rovira & Virgili, Pediat Nutr & Dev Res Unit, IISPV, Reus, Spain.
47Childrens Mem Hlth Inst, Neonatal Dept, Warsaw, Poland.
48North Carolina State Univ, Dept Biol Sci, Raleigh, NC USA.
49Soder Sjukhuset, Dept Clin Sci & Educ, Karolinska Inst, Stockholm, Sweden.
50Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden.
51CHC, Liege, Belgium.
52Univ Grenoble Alpes, INSERM, CNRS,IAB, Team Environm Epidemiol Appl Reprod & Resp Hlth, Grenoble, France.
53Duke Univ, Med Ctr, Dept Obstet & Gynecol, Raleigh, NC USA.
54Harvard Med Sch, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, Boston, MA 02115 USA.
55Univ Milan, San Paolo Hosp, Dept Pediat, Milan, Italy.
56Ctr Individualised Infect Med, CIIM, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany.
57TWINCORE, Ctr Expt & Clin Infect Res, Hannover, Germany.
58Univ Colorado, Dept Med, Sch Med, Div Biomed Informat & Personalized Med, Aurora, CO USA.
59Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA.
60Univ Memphis, Div Epidemiol Biostat & Environm Hlth, Memphis, TN 38152 USA.
61Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA.
62Univ Colorado, Dept Pediat, Sch Med, Anschutz Med Campus, Aurora, CO USA.
63CSIRO Hlth & Biosecur, Adelaide, SA, Australia.
64Univ Turku, Turku Inst Adv Studies, Turku, Finland.
65Karolinska Univ Hosp, Pediat Allergy & Pulmonol Unit, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.
66Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
67Oulu Univ Hosp, Unit Primary Hlth Care, Oulu, Finland.
68Brunel Univ London, Coll Hlth & Life Sci, Dept Life Sci, London, England.
69Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Med & Hlth Sci, Dept Publ Hlth,Sect Epidemiol, Copenhagen, Denmark.
70Univ Western Australia, Telethon Kids Inst, Perth, WA, Australia.
71David Hide Asthma & Allergy Res Ctr, Newport, Wight, England.
72Norwegian Inst Publ Hlth, Dept Chron Dis & Ageing, Oslo, Norway.
73Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
74Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada.
75Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
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Language: English
Published: Springer Nature, 2020
Publish Date: 2021-03-10


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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Series: Genome medicine
ISSN: 1756-994X
ISSN-E: 1756-994X
ISSN-L: 1756-994X
Volume: 12
Issue: 1
Article number: 105
DOI: 10.1186/s13073-020-00810-w
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: The work on this meta-analysis received funding from the European Union’s Horizon 2020 research and innovation program (733206, LIFECYCLE; 633595, DynaHEALTH) and from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw, the Netherlands, no.529051022). Funding statements for all participating studies can be found in Additional file 2: Supplementary Methods.
EU Grant Number: (733206) LIFECYCLE - Early-life stressors and LifeCycle health
(633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
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