Parental body mass index and offspring childhood body size and eating behaviour: causal inference via parental comparisons and extended children of twins structural equation modelling

Background The intergenerational transmission of obesity-related traits could propagate an accelerating cycle of obesity, if parental adiposity causally influences offspring adiposity via intrauterine or periconceptional mechanisms. We aimed to establish whether associations between parental peri-pregnancy body mass index (BMI) and offspring birth weight (BW), BMI until 8 years and 8-year eating behaviour are due to genetic confounding. Methods We used data from the Norwegian Mother, Father and Child Cohort Study and the Medical Birth Registry of Norway. We compared the strength of the associations of maternal versus paternal BMI with offspring outcomes, and used an extended children of twins structural equation model (SEM) to quantify the extent to which associations were due to genetic confounding (n = 17001 to 85866 children). Findings Maternal BMI was more strongly associated than paternal BMI with offspring BW, but the maternal-paternal difference decreased for offspring BMI after birth. Greater parental BMI was associated with obesity-related offspring eating behaviours. SEM results indicated that genetic confounding did not explain the association between parental BMI and offspring BW, but explained the majority of the association with offspring BMI from 6 months onwards. For 8-year BMI, genetic confounding explained 79% (95% CI: 62%, 95%) of the covariance with maternal BMI and 94% (95% CI: 72%, 113%) of the covariance with paternal BMI. Interpretation We found strong evidence that parent-child BMI associations are primarily due to genetic confounding, arguing against a strong causal effect of maternal or paternal adiposity on childhood adiposity via intrauterine or periconceptional mechanisms. ### Competing Interest Statement DAL received support from Medtronic Ltd and Roche Diagnostics for research unrelated to that presented here. All other authors report no conflict of interest. ### Funding Statement The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this on-going cohort study. TAB, GDS, DAL, NMW and DME work in or are affiliated a unit that receives support from the University of Bristol and UK Medical Research Council (MC\_UU\_00011/1 and MC\_UU\_00011/6). This study has received support from the British Heart Foundation Accelerator Award at the University of Bristol (AA/18/1/34219) and a University of Queensland-University of Exeter Accelerator grant. LJH was supported by the South-Eastern Norway Regional Health Authority (2018058, 2019097) during the completion of this work. NMW is funded by a NHMRC Investigator grant (APP2008723). DME is funded by an Australian National Health and Medical Research Council Senior Research Fellowship (APP1137714) and this work was funded by National Health and Medical Research Council (Australia) (NHMRC) project grants (GNT1157714, GNT1183074). FAT was partly supported by the Research Council of Norway through its Centers of Excellence funding scheme (262700). ZA is funded by a Marie Skłodowska-Curie Fellowship from the European Research Council (894675). TAM is supported by a Wellcome Trust Senior Research Fellowship (220382/Z/20/Z). AH was supported by grants from the Norwegian Research Council (274611, 3006668) and the South-Eastern Norway Regional Health Authority (2018059, 2020022). EY was supported by the Research Council of Norway (288083). This paper is the work of the authors and does not necessarily represent the views of individuals or organizations acknowledged here. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of The Regional Committees for Medical and Health Research Ethics (Norway) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data from the Norwegian Mother, Father and Child Cohort Study and the Medical Birth Registry of Norway used in this study are managed by the national health register holders in Norway (Norwegian Institute of Public Health) and can be made available to researchers, subject to approval from the Regional Committees for Medical and Health Research Ethics (REC), compliance with the EU General Data Protection Regulation (GDPR) and approval from the data owners. The consent given by the participants does not cover storage of data on an individual level in repositories. Researchers who want access to data sets for replication should apply through helsedata.no. Access to data sets requires approval from The Regional Committee for Medical and Health Research Ethics in Norway and an agreement with MoBa.