Maternal seafood intake, dietary contaminant exposure, and risk of juvenile idiopathic arthritis: exploring gene-environment interactions

Front Immunol. 2025 Jan 14:15:1523990. doi: 10.3389/fimmu.2024.1523990. eCollection 2024.

Abstract

Objectives: Juvenile idiopathic arthritis (JIA) originates from a complex interplay between genetic and environmental factors. We investigated the association between seafood intake and dietary contaminant exposure during pregnancy and JIA risk, to identify sex differences and gene-environment interactions.

Methods: We used the Norwegian Mother, Father, and Child Cohort Study (MoBa), a population-based prospective pregnancy cohort (1999-2008). JIA patients were identified through the Norwegian Patient Registry, with remaining mother-child pairs serving as controls. We assessed maternal seafood intake and dietary contaminants typically found in seafood using a food frequency questionnaire completed during pregnancy, mainly comparing high (≥90th percentile, P90) vs low (<P90) intake. Multivariable logistic regression calculated adjusted odds ratios (aOR), including sex-stratification analyses. A polygenic risk score (PRS) for JIA was used in a subsample to assess gene-environment interactions.

Results: We identified 217 JIA patients and 71,884 controls. High vs low maternal intake of lean/semi-oily fish was associated with JIA (aOR 1.51, 95% CI 1.02-2.22), especially among boys (aOR 2.13, 95% CI 1.21-3.75). A significant gene-environment interaction was observed between total fish intake and PRS, with high fish intake associated with JIA primarily in those with low PRS (p<0.03). We found no associations between high vs low exposure to other types of seafood or environmental contaminants and JIA.

Conclusions: We found a modestly increased risk of JIA associated with high intake of lean/semi-oily fish during pregnancy, not explained by estimated exposure to dietary contaminants. Our data suggest a more pronounced association in children with a lower genetic predisposition for JIA.

Keywords: MoBa; contaminants; fish; gene-environment interaction; heavy metals; juvenile idiopathic arthritis (JIA); polygenic risk score; sex differences.

MeSH terms

  • Adult
  • Arthritis, Juvenile* / epidemiology
  • Arthritis, Juvenile* / etiology
  • Arthritis, Juvenile* / genetics
  • Child
  • Dietary Exposure / adverse effects
  • Female
  • Food Contamination
  • Gene-Environment Interaction*
  • Humans
  • Male
  • Maternal Exposure / adverse effects
  • Norway / epidemiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / epidemiology
  • Prenatal Exposure Delayed Effects / genetics
  • Prospective Studies
  • Risk Factors
  • Seafood* / adverse effects

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Our work has been financed through several public sources: Foundation DAM (grant number 2023/FO426544), South-Eastern Norway Regional Health Authority (grant number HSO/2023070) and Norwegian Rheumatology Association. LR and CW were supported by the intramural research program of the National Institute of Environmental Health Sciences, National Institutes of Health. The study was partly funded by the Research Council of Norway through its Centres of Excellence funding scheme (project No 262700).