炎症性肠病和虹膜睫状体炎之间的遗传重叠：来自欧洲人群全基因组关联研究的见解。

Genetic overlap between inflammatory bowel disease and iridocyclitis: insights from a genome-wide association study in a European population.

机构信息

Jiangxi University of Chinese Medicine, Nanchang, China.

Department of Anorectal Surgery, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China.

出版信息

BMC Genom Data. 2024 Oct 29;25(1):92. doi: 10.1186/s12863-024-01274-2.

DOI:10.1186/s12863-024-01274-2

PMID:39472800

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11520806/

Abstract

BACKGROUND

Inflammatory bowel disease (IBD) is occasionally associated with ophthalmic diseases, including iridocyclitis (IC). The co-occurrence of IBD and IC has been increasingly observed, possibly due to shared genetic structures.

METHODS

A three-part analysis was executed utilizing genome-wide association study (GWAS) data on IBD and IC. First, the overall genetic correlation between the two traits was observed using linkage disequilibrium score regression (LDSC). Subsequent to this, a local genetic correlation analysis was conducted utilizing the heritability estimation from summary statistics (HESS) methodology. Finally, the conditional/conjunctional false discovery rate (cond/conjFDR) statistical framework was utilized to ascertain the degree of genetic overlap between the two traits.

RESULTS

Positive overall correlations were observed among IBD, ulcerative colitis (UC), and IC, encompassing both acute/subacute and chronic IC presentations. While a significant correlation was identified between Crohn's disease (CD) and IC, it was not evident for acute/subacute or chronic IC (P > 0.05). Notably, IBD (encompassing CD and UC) demonstrated local genetic correlations with IC and acute/subacute IC, with pronounced enrichment notably on chromosomes 1 and 6, though such correlations were not observed with chronic IC. The conjFDR analysis confirmed the genetic overlap between the two diseases. The shared genes overlapping between IBD (encompassing CD and UC) and IC were IL23R, GPR35, and ERAP1. For acute/subacute IC and chronic IC, there were six overlapping genes (GPR35, RPL23AP12, IL23R, SNAPC4, ERAP1, and INAVA) and one overlapping gene (INAVA), respectively.

CONCLUSION

This study confirms the existence of a shared genetic structure between IBD and IC, providing a biological basis for their comorbidity. Additionally, this finding has significant implications for preventing and treating these two diseases.

摘要

背景

炎症性肠病（IBD）偶尔与眼部疾病相关，包括虹膜睫状体炎（IC）。IBD 和 IC 的同时发生越来越被观察到，这可能是由于共享的遗传结构。

方法

使用针对 IBD 和 IC 的全基因组关联研究（GWAS）数据执行了三部分分析。首先，使用连锁不平衡得分回归（LDSC）观察两个性状之间的总体遗传相关性。在此之后，利用从汇总统计数据中估计的遗传力（HESS）方法进行局部遗传相关性分析。最后，利用条件/联合虚假发现率（cond/conjFDR）统计框架来确定两个性状之间遗传重叠的程度。

结果

IBD、溃疡性结肠炎（UC）和 IC 之间观察到阳性的总体相关性，包括急性/亚急性和慢性 IC 表现。虽然在克罗恩病（CD）和 IC 之间发现了显著相关性，但在急性/亚急性或慢性 IC 中则不明显（P>0.05）。值得注意的是，IBD（包括 CD 和 UC）与 IC 和急性/亚急性 IC 显示出局部遗传相关性，在染色体 1 和 6 上表现出明显的富集，尽管与慢性 IC 则未观察到这种相关性。conjFDR 分析证实了两种疾病之间的遗传重叠。IBD（包括 CD 和 UC）和 IC 之间重叠的共享基因包括 IL23R、GPR35 和 ERAP1。对于急性/亚急性 IC 和慢性 IC，分别有六个重叠基因（GPR35、RPL23AP12、IL23R、SNAPC4、ERAP1 和 INAVA）和一个重叠基因（INAVA）。