University of Oulu

Tom A Bond, Ville Karhunen, Matthias Wielscher, Juha Auvinen, Minna Männikkö, Sirkka Keinänen-Kiukaanniemi, Marc J Gunter, Janine F Felix, Inga Prokopenko, Jian Yang, Peter M Visscher, David M Evans, Sylvain Sebert, Alex Lewin, Paul F O’Reilly, Debbie A Lawlor, Marjo-Riitta Jarvelin, Exploring the role of genetic confounding in the association between maternal and offspring body mass index: evidence from three birth cohorts, International Journal of Epidemiology, Volume 49, Issue 1, February 2020, Pages 233–243,

Exploring the role of genetic confounding in the association between maternal and offspring body mass index : evidence from three birth cohorts

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Author: Tom A Bond, Tom A.1; Karhunen, Ville1; Wielscher, Matthias1;
Organizations: 1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London , London, UK
2Oulunkaari Health Center , Ii, Finland
3Medical Research Center, Oulu University Hospital and University of Oulu , Oulu, Finland
4Center for Life-Course Health Research, Faculty of Medicine, University of Oulu , Oulu, Finland
5Northern Finland Birth Cohort, Faculty of Medicine, University of Oulu , Oulu, Finland
6Healthcare and Social Services of Selänne , Pyhäjärvi, Finland
7Section of Nutrition and Metabolism , IARC, Lyon, France
8The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam , Rotterdam, The Netherlands
9Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam , Rotterdam, The Netherlands
10Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam , Rotterdam, The Netherlands
11Section of Genomics of Common Disease, Department of Medicine, Imperial College London , London, UK
12Institute for Molecular Bioscience, University of Queensland , Brisbane, Australia
13Queensland Brain Institute, University of Queensland , Brisbane, Australia
14University of Queensland Diamantina Institute, Translational Research Institute , Brisbane, Australia
15MRC Integrative Epidemiology Unit at the University of Bristol , Bristol, UK
16Biocenter Oulu, University of Oulu , Oulu, Finland
17Department of Medical Statistics, London School of Hygiene and Tropical Medicine , London, UK
18MRC Social, Genetic and Developmental Psychiatry Centre, King’s College London , London, UK
19Population Health Science, Bristol Medical School , Bristol, UK
20Unit of Primary Care, Oulu University Hospital , Oulu, Finland
21Department of Life Sciences, College of Health and Life Sciences, Brunel University London , London, UK
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: Oxford University Press, 2020
Publish Date: 2020-07-02


Background: Maternal pre-pregnancy body mass index (BMI) is positively associated with offspring birth weight (BW) and BMI in childhood and adulthood. Each of these associations could be due to causal intrauterine effects, or confounding (genetic or environmental), or some combination of these. Here we estimate the extent to which the association between maternal BMI and offspring body size is explained by offspring genotype, as a first step towards establishing the importance of genetic confounding.

Methods: We examined the associations of maternal pre-pregnancy BMI with offspring BW and BMI at 1, 5, 10 and 15 years, in three European birth cohorts (n ≤11 498). Bivariate Genomic-relatedness-based Restricted Maximum Likelihood implemented in the GCTA software (GCTA-GREML) was used to estimate the extent to which phenotypic covariance was explained by offspring genotype as captured by common imputed single nucleotide polymorphisms (SNPs). We merged individual participant data from all cohorts, enabling calculation of pooled estimates.

Results: Phenotypic covariance (equivalent here to Pearson’s correlation coefficient) between maternal BMI and offspring phenotype was 0.15 [95% confidence interval (CI): 0.13, 0.17] for offspring BW, increasing to 0.29 (95% CI: 0.26, 0.31) for offspring 15 year BMI. Covariance explained by offspring genotype was negligible for BW [−0.04 (95% CI: −0.09, 0.01)], but increased to 0.12 (95% CI: 0.04, 0.21) at 15 years, which is equivalent to 43% (95% CI: 15%, 72%) of the phenotypic covariance. Sensitivity analyses using weight, BMI and ponderal index as the offspring phenotype at all ages showed similar results.

Conclusions: Offspring genotype explains a substantial fraction of the covariance between maternal BMI and offspring adolescent BMI. This is consistent with a potentially important role for genetic confounding as a driver of the maternal BMI–offspring BMI association.

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Series: International journal of epidemiology
ISSN: 0300-5771
ISSN-E: 1464-3685
ISSN-L: 0300-5771
Volume: 49
Issue: 1
Pages: 233 - 243
DOI: 10.1093/ije/dyz095
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
3111 Biomedicine
Funding: NFBC1966 and 1986 have received financial support from the Academy of Finland [EGEA, grant number: 285547]; University Hospital Oulu, Biocenter, University of Oulu, Finland [grant number: 75617; 2016-20]; NIHM [grant number: MH063706]; Juselius Foundation; NHLBI [grant number: 5R01HL087679-02] through the STAMPEED program [grant number: 1RL1MH083268-01]; the European Commission [EURO-BLCS, Framework 5 award QLG1-CT-2000-01643], the Medical Research Council, UK [grant numbers: MR/M013138/1, MRC/BBSRC, MR/S03658X/1 (JPI HDHL)]; the EU H2020 DynaHEALTH action [grant number: 633595]; the EU H2020-HCO-2004 iHEALTH Action [grant number: 643774]; the EU H2020-PHC-2014 ALEC Action [grant number: 633212]; the EU H2020-SC1-2016-2017 LifeCycle Action [grant number: 733206]; the EU H2020-MSCA-ITN-2016 CAPICE Action [grant number: 721567]. The DNA extractions, sample quality controls, biobank upkeep and aliquoting were performed in the National Public Health Institute, Biomedicum Helsinki, Finland and supported financially by the Academy of Finland and Biocentrum Helsinki. The UK Medical Research Council and Wellcome [grant number: 102215/2/13/2] and the University of Bristol provide core support for ALSPAC. Genotyping of the ALSPAC maternal samples was funded by the Wellcome Trust [grant number: WT088806] and the offspring samples were genotyped by Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This study was also supported by the US National Institute of Health [grant number: R01 DK10324] and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013) / ERC grant agreement [grant number: 669545]. A comprehensive list of grants funding is available on the ALSPAC website ( T.A.B. is supported by the Medical Research Council (UK) [grant number: MR/K501281/1]. D.M.E. and D.A.L. work in / are affiliated with a unit that is supported by the UK Medical Research Council [grant number: MC_UU_00011/6] and D.A.L. is a NIHR Senior Investigator [grant number: NF-SI-0611–10196]. I.P. is funded by the World Cancer Research Fund (WCRF UK) and World Cancer Research Fund International [grant number: 2017/1641] and the Wellcome Trust [grant number: WT205915].
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(643774) iHealth-T2D - Family-based intervention to improve healthy lifestyle and prevent Type 2 Diabetes amongst South Asians with central obesity and prediabetes
(733206) LIFECYCLE - Early-life stressors and LifeCycle health
Academy of Finland Grant Number: 285547
Detailed Information: 285547 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited