Higher prevalence of autism in offspring born to mothers with rheumatoid arthritis has been reported in observational studies. We investigated (a) the associations between maternal and offspring’s own genetic liability for rheumatoid arthritis and autism-related outcomes in the offspring using polygenic risk scores (PRS) and (b) whether the effects were causal using Mendelian randomization (MR). Using the latest genome-wide association (GWAS) summary data on rheumatoid arthritis and individual-level data from the Avon Longitudinal Study of Parents and Children, United Kingdom, we constructed PRSs for maternal and offspring genetic liability for rheumatoid arthritis (single-nucleotide polymorphism [SNP] p-value threshold 0.05). We investigated associations with autism, and autistic traits: social and communication difficulties, coherence, repetitive behaviours and sociability. We used modified Poisson regression with robust standard errors. In two-sample MR analyses, we used 40 genome-wide significant SNPs for rheumatoid arthritis and investigated the causal effects on risk for autism, in 18,381 cases and 27,969 controls of the Psychiatric Genetics Consortium and iPSYCH. Sample size ranged from 4992 to 7849 in PRS analyses. We found little evidence of associations between rheumatoid arthritis PRSs and autism-related phenotypes in the offspring (maternal PRS on autism: RR 0.89, 95%CI 0.73–1.07, p = 0.21; offspring’s own PRS on autism: RR 1.11, 95%CI 0.88–1.39, p = 0.39). MR results provided little evidence for a causal effect (IVW OR 1.01, 95%CI 0.98–1.04, p = 0.56). There was little evidence for associations between genetic liability for rheumatoid arthritis on autism-related outcomes in offspring. Lifetime risk for rheumatoid arthritis has no causal effects on autism.
|Number of pages||6|
|Publication status||Published - 12 Jan 2022|
Bibliographical noteFunding Information:
We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole Avon Longitudinal Parents and Children study team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/ Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and AL, DR, ES, BL, HJJ, and CD will serve as guarantors for the contents of this paper. Child GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andme. Mother GWAS data were generated using support from the Wellcome Trust (Grant ref: WT088806). A comprehensive list of grants’ funding is available on the ALSPAC website (http:// www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by numerous research grants. AL is funded by a 4-year Wellcome Trust studentship grant (Grant ref: 220059/Z/19/Z). CD is also funded by a 4-year Wellcome Trust studentship grant [108902/B/15/Z]. This research was also funded in part, by the Wellcome Trust (Grant ref: 204895/Z/16/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. BL was supported by the Wellcome Trust (Grant ref: 204895/Z/16/Z), with ES as one of the grant-award recipients. BL and ES work in a unit that receives funding from the University of Bristol and the UK Medical Research Council (Grant refs: MC_UU_00011/ 1 and MC_UU_00011/3). Regarding autism-related outcome research, DR is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol (Grant ref: BRC-1215-2011). HJJ is also supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The Wellcome Trust, as funders, played no role in study design; the collection, analysis, and interpretation of data; writing of this paper; and the decision to submit the article for publication.
© 2022, The Author(s).
- polygenic risk scores
- mendelian randomization
- rheumatoid arthritis
- autism spectrum disorder