Genetic and Non-Genetic Determinants of IBS

Association between IBS and nongenetic risk factors, including risk factors assayed by recall from the DHQ, was tested using logistic regression conditioning on age and sex (Supplementary Note, ‘Nongenetic associations’).
Standard genetic quality control was carried out to remove samples with poor genotype quality and variants with poor genotyping or imputation performance. Only participants of European ancestry were included in the discovery dataset due to the limited number of non-European ancestry participants. GWAS were conducted using a linear mixed model (BOLT-LMM v.2.3.2)^{53 (link)} to control for population stratification and relatedness. Meta-analysis of GWAS summary statistics was carried out using METAL (March 2011 release)^{54 (link)}. The UKB GWAS was stratified into DHQ respondents and nonrespondents, with results meta-analyzed to avoid genetic confounding with questionnaire response (Supplementary Fig. 14).
We assigned loci to candidate genes using annotations from FUMA v.1.3.4^{55 (link)}, as well as from a colocalization analysis using Coloc v.3.2-1^{56 (link)} on multi-tissue expression data from the Genotype-Tissue Expression (GTEx) consortium^{56 (link),57 (link)}. We calculated SNP heritability and coheritability (r_g, genetic correlation) using univariate and bivariate LDSC^{48 (link)} against a range of traits via the LD Hub website^{33 (link)}. Other statistical analyses were carried out using R v.3.6.1; any P values were obtained from two-sided tests unless otherwise specified.

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Eijsbouts C., Zheng T., Kennedy N.A., Bonfiglio F., Anderson C.A., Moutsianas L., Holliday J., Shi J., Shringarpure S., Voda A.I., Farrugia G., Franke A., Hübenthal M., Abecasis G., Zawistowski M., Skogholt A.H., Ness-Jensen E., Hveem K., Esko T., Teder-Laving M., Zhernakova A., Camilleri M., Boeckxstaens G., Whorwell P.J., Spiller R., McVean G., D’Amato M., Jostins L, & Parkes M. (2021). Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nature Genetics, 53(11), 1543-1552.

Publication 2021

Correlation European Genes loci Genetic control Genotype Gwas Metal Nonrespondents Recall Tissue

Corresponding Organization : University of Cambridge

Other organizations : Karolinska Institutet, University of Exeter, Wellcome Sanger Institute, 23andMe (United States), Mayo Clinic in Arizona, University of California, Los Angeles, Neurobehavioral Systems, University of Washington, Washington University in St. Louis, University of North Carolina at Chapel Hill, Michigan Medicine, University of Arizona, Texas Children's Hospital, Baylor College of Medicine, University of the Basque Country, Karolinska University Hospital, Umeå University, Skåne University Hospital, Lund University, Linköping University, University of Gothenburg, Örebro University, University of Bari Aldo Moro, Policlinico S.Orsola-Malpighi, University of Bologna, Azienda Ospedaliera G. Brotzu, University of Chieti-Pescara, Federico II University Hospital, Ospedale Sant'Anna, University of Padua, University of Pisa, Casa Sollievo della Sofferenza, St James's University Hospital, University of Leeds, Maastricht University, University Medical Center Groningen, Radboud University Nijmegen, Radboud University Medical Center, University Hospital Heidelberg, Heidelberg University, Israelitisches Krankenhaus, Helios Klinikum Krefeld, University Hospital of Basel, Kiel University, University of Bergen, NORCE Norwegian Research Centre, Norwegian University of Science and Technology, Florey Institute of Neuroscience and Mental Health, KU Leuven, University Hospital Schleswig-Holstein, University of Lübeck, University of Michigan–Ann Arbor, University of Tartu, Mayo Clinic, Wythenshawe Hospital, University of Manchester, National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham

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Protocol cited in 14 other protocols

Variable analysis

independent variables

Nongenetic risk factors, including risk factors assayed by recall from the DHQ

dependent variables

IBS (Irritable Bowel Syndrome)

controls

Positive control: None specified
Negative control: None specified

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