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Background & Aims The association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization of complex trait-associated loci and may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profiles of colon mucosa gene expression and alternative splicing and compare them across colon subsites (ascending, transverse, and descending), (2) to identify expression and splicing quantitative trait loci (QTLs), (3) to find traits for which identified QTLs contribute to single-nucleotide polymorphism (SNP)-based heritability, (4) to propose candidate effector genes, and (5) to provide a web-based visualization resource. Methods We collected colonic mucosal biopsy specimens from 485 healthy adults and performed bulk RNA sequencing. We performed genome-wide SNP genotyping from blood leukocytes. Statistical approaches and bioinformatics software were used for QTL identification and downstream analyses. Results We provided a complete quantification of gene expression and alternative splicing across colon subsites and described their differences. We identified thousands of expression and splicing QTLs and defined their enrichment at genome-wide regulatory regions. We found that part of the SNP-based heritability of diseases affecting colon tissue, such as colorectal cancer and inflammatory bowel disease, but also of diseases affecting other tissues, such as psychiatric conditions, can be explained by the identified QTLs. We provided candidate effector genes for multiple phenotypes. Finally, we provided the Colon Transcriptome Explorer web application. Conclusions We provide a large characterization of gene expression and splicing across colon subsites. Our findings provide greater etiologic insight into complex traits and diseases influenced by transcriptomic changes in colon tissue.

Background The most common side effect in population screening programmes is a false-positive result which leads to unnecessary risks and costs. Aims To identify factors associated with false-positive results in a colorectal cancer screening programme with the faecal immunochemical test (FIT). Methods Cross-sectional study of 472 participants with a positive FIT who underwent colonoscopy for confirmation of diagnosis between 2013 and 2014. A false-positive result was defined as having a positive FIT (≥20 μg haemoglobin per gram of faeces) and follow-up colonoscopy without intermediate/high-risk lesions or cancer. Results Women showed a two-fold increased likelihood of a false-positive result compared with men (adjusted OR, 2.3; 95%CI, 1.5–3.4), but no female-specific factor was identified. The other variables associated with a false-positive result were successive screening (adjusted OR, 1.5; 95%CI, 1.0–2.2), anal disorders (adjusted OR, 3.1; 95%CI, 2.1–4.5) and the use of proton pump inhibitors (adjusted OR, 1.8; 95%CI, 1.1–2.9). Successive screening and proton pump inhibitor use were associated with FP in men. None of the other drugs were related to a false-positive FIT. Conclusion Concurrent use of proton pump inhibitors at the time of FIT might increase the likelihood of a false-positive result. Further investigation is needed to determine whether discontinuing them could decrease the false-positive rate.