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. 2023 Aug 10;24(9):1540–1551. doi: 10.1038/s41590-023-01588-w

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — a, Genetic associations in the CXCL5 gene region. From top to bottom: plasma CXCL5 pQTL (n = 14,824 participants), whole-blood eQTL (from eQTLGen data, n = 31,684 participants), colon tissue eQTL (GTEx, n = 368 individuals), UC (cases = 12,366, controls = 33,609) and CD (cases = 12,194, controls = 28,072) (from the IBD Genetics Consortium⁵¹). The purple diamond shows the sentinel pQTL variant. Other variants are colored by LD to the sentinel pQTL. P values are from linear regression for QTLs and logistic regression for case-control GWAS. b, Violin plots showing CXCL5 expression in gut mucosal samples from patients with UC or CD and healthy controls (HC) in IBD TaMMA. c, Volcano plot showing differential expression analysis comparing colonic tissue from UC with HCs (IBD TaMMA). Red and blue points represent significantly (5% FDR) up- and downregulated transcripts, respectively. Gray indicates nonsignificant. P_BH, Benjamini–Hochberg adjusted P values. P values in c and d are from Wald tests (two sided). d, Replication. Left, CXCL5 differential expression in colon biopsies in UC versus HCs from transcriptome-wide analysis across three cohorts. The GSE numbers are GEO accession numbers. Imperial is the Imperial UC cohort. Each lollipop represents a separate cohort: GSE16879 (n = 24 UC patients versus n = 6 HCs); GSE206285 (n = 550 UC patients versus n = 18 HCs); and Imperial (n = 16 UC versus 6 HCs). The circle color indicates the log₂(FC) in CXCL5 expression between UC and HCs. Right, CXCL5 expression in colon biopsies sampled at baseline during the UNIFI clinical trial. Each point represents an individual. e, Forest plot showing MR analysis for UC and CD. OR is the odds ratio for the risk associated with a 1 s.d. increase in the level of the protein. The center of the bar is the point estimate for OR and the whiskers are the 95% CIs.