![]() ![]() The association of uncommon protein-altering mutations that are expected to impart a higher risk of disease may help to explain some of the missing heritability in IBD. The success of the GWAS approach is supported by the link between neighboring common variations in human populations, but it also makes it challenging to determine with accuracy which variant is causative, the molecular consequences of that variant, and frequently even which gene is perturbed. Genome-wide association studies (GWAS) that look for genetic factors influencing disease start and progression have found 240 IBD-associated loci, which have greatly improved our understanding of the biology underlying these conditions ( Anderson et al., 2011 de Lange et al., 2017 de Lange et al., 2017 Franke et al., 2010 Liu et al., 2015). Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis, is a complex polygenic disorder brought on by the improper activation of effector immunologic pathways in those with a genetic predisposition. The functional mechanism of SIRPB1 and its downstream inflammatory pathways was preliminarily explored in CD. Additionally, it promoted the synthesis of the pro-inflammatory cytokines IL-1, TNF-, and IL-6.Ĭonclusion: Our results suggest that the rare gain-of-function frameshift variant in SIRPB1 is associated in Han Chinese patients with CD. The frameshift variation induced tyrosine phosphorylation of Syk, Akt, and Jak2, elevated the expression of SIRPB1 at the mRNA and protein levels, activated DAP12, and controlled the activation of NF-κB in macrophages. As a result, patients carrying a rare frameshift variant (c.1143_1144insG p. Among them, 61 candidate loci were validated in replication analyses. Results: There were 92 genetic variants significantly associated with CD in Chinese individuals. Replication analyses were performed in an independent cohort including 381 patients with CD and 381 control subjects. Materials and methods: We performed family-based genome sequencing (WGS) analysis on 24 patients with CD from 12 families and then filtered shared potential causal variants by incorporating association results from meta-analyses of CD GWAS and immunology genes and in silico variant effect prediction algorithms. With a focus on Han Chinese families with CD, the aim of this study was to find genetic variations that increase CD susceptibility by genome sequencing, genetic association, expression, and functional research. 4Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Chinaīackground: Crohn’s disease (CD), a chronic gastrointestinal inflammatory disease, is increasing in China. ![]() 3Institute of Biomedical Sciences, SequMed Biotech Inc., Guangzhou, China.2Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.1Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.Jian Tang 1 †, Xingyang Wan 2 †, JunXiao Zhang 3 †, Na Diao 1, Caibin Zhang 4, Xiang Gao 1* and Donglin Ren 2* ![]()
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