X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans

Abstract

Background and Aims: Genome-wide association studies of inflammatory bowel disease identified > 200 susceptibility loci only in autosomes. This study aimed to identify inflammatory bowel disease susceptibility loci on the X chromosome. Methods: We performed an X chromosome-wide association study in Korean patients with inflammatory bowel disease. We analysed X chromosome data from our recent genome-wide association studies, including 1505 cases [922 Crohn's disease and 583 ulcerative colitis] and 4041 controls during the discovery phase, followed by replication in additional 1989 cases [993 Crohn's disease, 996 ulcerative colitis] and 3491 controls. Sex-related differential effects of single nucleotide polymorphisms on disease were also evaluated. Results: We confirmed a significant association of a previously reported inflammatory bowel disease susceptibility locus at chromosome Xq26.3 [CD40LG-ARHGEF6; odds ratio, 1.22; 95% confidence interval, 1.16-1.28; combined p = 3.79 × 10]. This locus accounted for 0.18% and 0.12% of genetic variance in Crohn's disease and ulcerative colitis, respectively, and increased the total autosomal chromosome genetic variance from 6.65% to 6.83% and from 5.47% to 5.59% for Crohn's disease and ulcerative colitis risk, respectively, in the Korean population. Sex-stratified analyses did not reveal sex-related differences in effect sizes. Conclusions:We confirmed the association of rs2427870 at the CD40LG-ARHGEF6 locus with an inflammatory bowel disease through an X chromosome-wide association study in a Korean Downloaded from https://academic.oup.com/ecco-jcc/article-abstract/11/7/820/3041097 by guest on 07 June 2019 population. Our data suggest that the CD40LG-ARHGEF6 locus on the X chromosome might play a role in inflammatory bowel disease pathogenesis in the Korean population.

Joint identification of sex and sex‐linked scaffolds in non‐model organisms using low depth sequencing data

“…The benefits of identifying sex-linked scaffolds when carrying out population genetic studies are many. First, sex chromosomal sites may be desirable for specific analyses, such as association (Lee et al, 2017;Luciano et al, 2021;Zuo et al, 2013), gene expression (Grath & Parsch, 2016), or any evolutionary genetic studies on X/Y or Z/W chromosomes (Gottipati et al, 2011). Second, if sex-linked scaffolds are not flagged and treated separately they may bias analyses such as demographic history inference (Li & Durbin, 2011), genome scans or genome-wide values of summary statistics, including F ST (Lambert et al, 2010), genetic diversity (Hammer et al, 2010) and allele frequency distribution (Clayton, 2008).…”

Impact of Female Gender in Inflammatory Bowel Diseases: A Narrative Review

“…The female genetic predisposition to develop IBD is also related to X chromosome abnormalities, such as Turner syndrome [ 25 ]. In IBD-affected relative pairs, X-linked susceptibility loci have been identified [ 26 , 27 ]. In a murine model, the loss of one allele of the Cosmc X-linked gene evoked gut dysbiosis, enhanced experimental colitis, and a spatial pattern of dysbiosis resembling IBD in males but not in female mice.…”

Increased prevalence of migraine in women with inflammatory bowel disease: A cross-sectional study

“…There are other factors which could contribute to this association. The association between migraine and IBD was only significant for females, which could suggest a role for sex-linked factors, such as oestrogens (31,32) or even genetic predisposition depending on sexual chromosomes (33). On the other hand, non-steroidal antiinflammatory agents are the most popular acute treatment of migraine and they have been shown to have the potential to trigger the onset or relapse of IBD (34).…”