Mendelian randomization study reveals a causal relationship between body mass index in children and risk of autoimmune diseases

Medicine (Baltimore). 2024 Oct 11;103(41):e40094. doi: 10.1097/MD.0000000000040094.

Abstract

Newly emerging evidence indicates that body mass index (BMI) is a potential risk factor for autoimmune diseases (ADs). Nevertheless, the exact causal connection between ADs and BMI in children remains uncertain. To investigate the relationship between BMI in children and ADs, a 2-sample Mendelian randomization (MR) analysis was conducted. In this analysis, several regression methods were utilized, including the inverse-variance weighted (IVW), weighted mode, weighted median, and MR-Egger regression. Publicly available summary statistics datasets from meta-analyses of genome-wide association studies (GWAS) were employed, specifically focusing on BMI in children of European descent (n = 39,620) from the UK Biobank (ebi-a-GCST90002409) as the exposure group. The outcomes were derived from individuals included in the Finnish biobank study FinnGen, with 42,202 cases and 176,590 controls representing the ADs group (finngen_R5_AUTOIMMUNE). For instrumental variables, we carefully selected 16 single nucleotide polymorphisms (SNPs) from GWAS on BMI in children. Our analysis implemented the IVW method, which demonstrated supporting evidence for a causal association between BMI in children and ADs. The results indicated a significant effect with a beta coefficient of 0.22, standard error (SE) of 0.05, odds ratio (OR) of 1.25, and a 95% confidence interval (CI) ranging from 1.13 to 1.38, with a P-value of <.05. We also utilized the weighted median method, which yielded similar findings to the IVW method. The OR estimates from the weighted median analysis showed a beta coefficient of 0.20, SE of 0.06, OR of 1.22, and a 95% CI ranging from 1.08 to 1.36, with a P-value of <.05. No significant association was observed in the MR-Egger and Weighted mode analyses. The findings from the MR analysis suggest that there is evidence supporting a potential causal link between BMI in children and an increased susceptibility to ADs.

MeSH terms

  • Autoimmune Diseases* / epidemiology
  • Autoimmune Diseases* / genetics
  • Body Mass Index*
  • Child
  • Female
  • Finland / epidemiology
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Mendelian Randomization Analysis*
  • Polymorphism, Single Nucleotide*
  • Risk Factors