Projects per year
Abstract
Evidence linking parental diagnoses of inflammatory bowel disease (IBD) with offspring autism is inconclusive. We conducted four complementary studies to investigate associations between parental diagnoses of IBD and offspring autism and elucidate their underlying aetiology. (1) Nationwide population-based cohort study using Swedish registers to examine associations between parental IBD diagnoses and autism diagnoses in offspring, (2) Linkage disequilibrium (LD)-score regression to estimate the genetic correlation between the phenotypes. (3) Polygenic risk score (PRS) analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate associations between maternal genetic liability to IBD and autism factor mean score in offspring. (4) Two-sample Mendelian randomization (MR) to assess bidirectional causal links between genetic liability to IBD and autism. We found evidence of an association between parental IBD diagnoses and offspring autism (maternal: OR= 1.32; 95% CI: 1.25 to 1.40; p<0.001; paternal: OR= 1.09; 95% CI: 1.02 to 1.17; p=0.012; n= 2 324 227, 52.3% male). PRS analyses in ALSPAC indicated associations between maternal PRS for IBD subtypes and a measure of broad autism phenotype, autism factor mean score, in the offspring (UC: βPRS= 0.02; 95%CI: 0.003 to 0.05; p= 0.02; R2=0.06; Crohn’s: βPRS= 0.03; 95%CI: 0.01 to 0.05; p= 0.004; R2= 0.06; n= 7348, 50.3% male). MR analyses provided evidence of a potential causal effect of genetic liability for IBD, especially ulcerative colitis, on autism (ORMR= 1.03; 95%CI: 1.01 to 1.06). Triangulating evidence from a nationwide register-based cohort study, genetic correlation, polygenic risk score analyses and MR, we found evidence of a potentially causal link between parental, particularly maternal, diagnoses and genetic liability to IBD and offspring autism. Perinatal immune system dysregulation, micronutrient malabsorption and anaemia may be implicated.
Original language | English |
---|---|
Pages (from-to) | 1406-1411 |
Number of pages | 6 |
Journal | Nature Medicine |
Volume | 28 |
Issue number | 7 |
Early online date | 2 Jun 2022 |
DOIs | |
Publication status | E-pub ahead of print - 2 Jun 2022 |
Bibliographical note
Funding Information:The Medical Research Council (MRC) and the University of Bristol support the MRC Integrative Epidemiology Unit (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/5, MC_UU_00011/6; P.P., A.H., E.S., G.M.K., H.J.J., G.D.S.). G.D.S., H.J., D.R., S.S., and S.Z. are supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. C. Dardani acknowledges the support of Wellcome Trust (215379/Z/19/Z). G.M.K. acknowledges funding support from the Wellcome Trust (201486/Z/16/Z), and the MRC UK (MR/W014416/1 and MR/S037675/1). The iPSYCH team was supported by grants from the Lundbeck Foundation (R102-A9118, R155-2014-1724, and R248-2017-2003), NIMH (1U01MH109514-01), and the Universities and University Hospitals of Aarhus and Copenhagen. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Center for Integrative Sequencing, iSEQ, Aarhus University, Denmark. R.G. acknowledges funding support from the Swedish Research Council (VR2017-02900). A.H. was supported by grants from the southeastern Norway Regional Health Authority (2020022, 2018059) and the Research Council of Norway (274611, 288083). H.K. is supported by grants from the Swedish Research Council (2018-02907) and Hjärnfonden (FO2020-0019). C. Dalman acknowledges funding from the Swedish Research Council (523-2010-1052) to support the Psychiatry Sweden register linkage and for further support of studies of the role of the early life immune system in autism (2021-01306). The UK Medical Research Council and Wellcome [Grant ref: 217065/Z/19/Z] and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. 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 ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.
Funding Information:
The Medical Research Council (MRC) and the University of Bristol support the MRC Integrative Epidemiology Unit (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/5, MC_UU_00011/6; P.P., A.H., E.S., G.M.K., H.J.J., G.D.S.). G.D.S., H.J., D.R., S.S., and S.Z. are supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. C. Dardani acknowledges the support of Wellcome Trust (215379/Z/19/Z). G.M.K. acknowledges funding support from the Wellcome Trust (201486/Z/16/Z), and the MRC UK (MR/W014416/1 and MR/S037675/1). The iPSYCH team was supported by grants from the Lundbeck Foundation (R102-A9118, R155-2014-1724, and R248-2017-2003), NIMH (1U01MH109514-01), and the Universities and University Hospitals of Aarhus and Copenhagen. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Center for Integrative Sequencing, iSEQ, Aarhus University, Denmark. R.G. acknowledges funding support from the Swedish Research Council (VR2017-02900). A.H. was supported by grants from the southeastern Norway Regional Health Authority (2020022, 2018059) and the Research Council of Norway (274611, 288083). H.K. is supported by grants from the Swedish Research Council (2018-02907) and Hjärnfonden (FO2020-0019). C. Dalman acknowledges funding from the Swedish Research Council (523-2010-1052) to support the Psychiatry Sweden register linkage and for further support of studies of the role of the early life immune system in autism (2021-01306). The UK Medical Research Council and Wellcome [Grant ref: 217065/Z/19/Z] and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. 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 ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.
Publisher Copyright:
© 2022, The Author(s).
Fingerprint
Dive into the research topics of 'Parental inflammatory bowel disease and autism in children: Triangulating the evidence using four complementary study designs'. Together they form a unique fingerprint.Projects
- 3 Finished
-
IEU 2 Relton Programme - Epigenetic Epidemiology
Relton, C. L. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research
-
Rework of IEU 2 Tilling Programme
Tilling, K. M. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research
-
IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research