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| Home > Articles > Published articles > Prenatal environmental exposures associated with sex differences in childhood obesity and neurodevelopment |
(Universitat Politècnica de Catalunya. Escola d'Enginyeria de Barcelona Est) (Barcelona Institute for Global Health (ISGlobal)) (Centre de Regulació Genòmica) (Fundación Pública Galega de Medicina Xenómica) (Vytautas Magnus University. Department of Environmental Science) (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut) (Universitat Autònoma de Barcelona. Departament de Matemàtiques)
| Date: | 2023 |
| Abstract: | Obesity and neurodevelopmental delay are complex traits that often co-occur and differ between boys and girls. Prenatal exposures are believed to influence children's obesity, but it is unknown whether exposures of pregnant mothers can confer a different risk of obesity between sexes, and whether they can affect neurodevelopment. We analyzed data from 1044 children from the HELIX project, comprising 93 exposures during pregnancy, and clinical, neuropsychological, and methylation data during childhood (5-11 years). Using exposome-wide interaction analyses, we identified prenatal exposures with the highest sexual dimorphism in obesity risk, which were used to create a multiexposure profile. We applied causal random forest to classify individuals into two environments: E1 and E0. E1 consists of a combination of exposure levels where girls have significantly less risk of obesity than boys, as compared to E0, which consists of the remaining combination of exposure levels. We investigated whether the association between sex and neurodevelopmental delay also differed between E0 and E1. We used methylation data to perform an epigenome-wide association study between the environments to see the effect of belonging to E1 or E0 at the molecular level. We observed that E1 was defined by the combination of low dairy consumption, non-smokers' cotinine levels in blood, low facility richness, and the presence of green spaces during pregnancy (OR = 0. 070, P = 2. 59 × 10 −5). E1 was also associated with a lower risk of neurodevelopmental delay in girls, based on neuropsychological tests of non-verbal intelligence (OR = 0. 42, P = 0. 047) and working memory (OR = 0. 31, P = 0. 02). In line with this, several neurodevelopmental functions were enriched in significant differentially methylated probes between E1 and E0. The risk of obesity can be different for boys and girls in certain prenatal environments. We identified an environment combining four exposure levels that protect girls from obesity and neurodevelopment delay. The combination of single exposures into multiexposure profiles using causal inference can help determine populations at risk. |
| Grants: | European Commission 308333 European Commission 874583 European Commission 211250 European Commission 226285 Agencia Estatal de Investigación CEX2018-000806-S |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Prenatal environment ; Sexual dimorphism ; Childhood obesity ; Neurodevelopment ; DNA methylation ; Causal inference ; Multiexposure profile |
| Published in: | BMC Medicine, Vol. 21 (April 2023) , art. 142, ISSN 1741-7015 |
