Genetic liability for rheumatic arthritis (RA) does not appear to affect autism-related outcomes in offspring, according to study results published in Translational Psychiatry.

Researchers aimed to study the associations between genetic liability for RA and autism-related outcomes in the offspring, and whether these effects were causal. Study participants included mothers and index offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Data were assessed using polygenic risk score (PRS)-generated correlations between mothers’ and offsprings’ genetic risk for autism- and RA-related outcomes in offspring, as well as Mendelian randomization (MR) for causality.

Researchers used the latest genome-wide association (GWAS) summary data in conjunction with ALSPAC data to construct PRSs for RA risk among mothers and offspring (single-nucleotide polymorphism [SNP] P-value threshold =.05) and also examined associations with autism and autism-related traits (repetitive behaviors, coherence, sociability, and communication and social difficulties). Modified Poisson regression was used with robust standard errors. In addition, 2-sample MR analyses were used with 40 genome-wide SNPs to investigate the causal effects of RA on the risk for autism.


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Autism was identified among 1.29% (n=101) of child participants who underwent genotyping analysis. Rheumatoid arthritis PRSs among mothers were not significantly associated with offsprings’ autism-related phenotypes (mothers’ autism PRS, 0.89 [95% CI, 0.73-1.07; P =.21]; offspring autism PRS, 1.11 [95% CI, 0.88-1.39; P =.39]). Performing MR assessments resulted in no clear evidence for a causal effect (odds ratio, 1.01; 95% CI, 0.98-1.04; P =.56).

Study limitations included potential confounding due to population stratification in GWAS summary statistics, a lack of risk for autism associated with de novo and rare genetic variants, potential selection bias, and the inability to interrogate the fetal programming hypothesis.

The study researchers concluded, “After investigating the effects of maternal and offspring’s own genetic liability for [RA] on autism-related phenotypes in offspring, we found little evidence for any associations.” In MR analyses, the study researchers “did not find any strong evidence of causal effects.”

Reference

Ly A, Leppert B, Rai D, Jones H, Dardani C, Stergiakouli E. Genetic liability to rheumatoid arthritis on autism and autistic traits: polygenic risk score and Mendelian randomization analyses. Transl Psychiatry. Published online January 12, 2022. doi:10.1038/s41398-021-01772-2