{"title":"Genetic overlap between inflammatory bowel disease and iridocyclitis: insights from a genome-wide association study in a European population.","authors":"Wu Liao, Qinghua Luo, Leichang Zhang, Haiyan Wang, Wei Ge, Jiawen Wang, Zhengyun Zuo","doi":"10.1186/s12863-024-01274-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":72427,"journal":{"name":"BMC genomic data","volume":"25 1","pages":"92"},"PeriodicalIF":1.9000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520806/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC genomic data","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s12863-024-01274-2","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
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.
背景：炎症性肠病（IBD）偶尔与眼科疾病相关，包括虹膜睫状体炎（IC）。人们越来越多地观察到 IBD 和 IC 同时发生，这可能是由于两者具有共同的遗传结构：方法：利用有关 IBD 和 IC 的全基因组关联研究（GWAS）数据进行了三部分分析。方法：利用 IBD 和 IC 的全基因组关联研究（GWAS）数据进行了三部分分析。首先，利用关联不平衡得分回归法（LDSC）观察了这两个性状之间的整体遗传相关性。随后，利用遗传率估计汇总统计（HESS）方法进行了局部遗传相关性分析。最后，利用条件/连接假发现率（cond/conjFDR）统计框架确定两个性状之间的遗传重叠程度：结果：在 IBD、溃疡性结肠炎（UC）和 IC（包括急性/亚急性和慢性 IC）之间观察到了整体正相关。虽然克罗恩病（CD）和慢性结肠炎之间存在明显的相关性，但急性/亚急性和慢性结肠炎之间的相关性并不明显（P > 0.05）。值得注意的是，IBD（包括 CD 和 UC）与 IC 和急性/亚急性 IC 存在局部遗传相关性，特别是在 1 号和 6 号染色体上有明显的富集，但与慢性 IC 没有观察到这种相关性。conjFDR 分析证实了这两种疾病的基因重叠。IBD（包括 CD 和 UC）和 IC 之间重叠的共有基因是 IL23R、GPR35 和 ERAP1。对于急性/亚急性 IC 和慢性 IC，分别有 6 个重叠基因（GPR35、RPL23AP12、IL23R、SNAPC4、ERAP1 和 INAVA）和 1 个重叠基因（INAVA）：这项研究证实了 IBD 和 IC 之间存在共同的遗传结构，为它们的合并症提供了生物学基础。此外，这一发现对预防和治疗这两种疾病具有重要意义。
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