{"title":"对炎症性肠病与阿尔茨海默病之间联系的孟德尔随机化和遗传多效性分析。","authors":"Yuxuan Wu, Yu Yan, Jike Qi, Yuxin Liu, Ting Wang, Hao Chen, Xinying Guan, Chu Zheng, Ping Zeng","doi":"10.1016/j.pnpbp.2024.111203","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The gut-microbiome-brain axis (GMBA) implies the connection between inflammatory bowel disease (IBD) and Alzheimer's disease (AD). We aimed to comprehensively explore the relation between IBD (and its subtypes) and AD, early-onset AD (EOAD) and late-onset AD (LOAD) from a genetic pleiotropy perspective.</p><p><strong>Methods: </strong>Relying on summary statistics (N = 472,868 for AD, 185,204 for EOAD, 191,061 for LOAD, 59,957 for IBD, 45,975 for CD, and 40,266 for UC), we first performed Mendelian Randomization to examine the causal association between IBD and AD by leveraging vertical pleiotropy. Then, we estimated global and local genetic correlations, followed by cross-trait association analysis to identify SNPs and genes with horizontal pleiotropy. Particularly, we utilized multi-trait colocalization analysis to assess the role of microbes in the common genetic etiology underlying the two types of diseases. Finally, we conducted functional enrichment analysis for pleiotropic genes.</p><p><strong>Results: </strong>We discovered suggestively causal relations between IBD (and its subtypes) and EOAD (OR<sub>IBD</sub> = 1.06 [1.01-1.11], OR<sub>CD</sub> = 1.05 [1.01-1.10], OR<sub>UC</sub> = 1.08 [1.01-1.15]) as well as between UC and LOAD (OR = 1.04 [1.01-1.08]), and discovered 44 local regions showing suggestively significant genetic correlations between IBD (and its subtypes) and AD (and EODA and LOAD). We further detected substantial genetic overlap, as characterized by 182 CE-associated, 3 EOAD-associated and 51 LOAD-associated pleiotropic SNPs as well as 291 pleiotropic genes. Pleiotropic genes more likely enriched in the GMBA-relevant tissues such as brain, intestine and esophagus. Moreover, we identified three microorganisms related to these disease pairs, including the Catenibacterium, Clostridia, and Prevotella species.</p><p><strong>Conclusion: </strong>The suggestively causal associations and shared genetic basis between IBD and its subtypes with AD, EOAD and LOAD may commonly drive their co-occurrence, and gut microbes might partly explain the shared genetic etiology. Further studies are warranted to elaborate the possibly biological mechanisms underlying the two types of diseases.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111203"},"PeriodicalIF":5.3000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mendelian randomization and genetic pleiotropy analysis for the connection between inflammatory bowel disease and Alzheimer's disease.\",\"authors\":\"Yuxuan Wu, Yu Yan, Jike Qi, Yuxin Liu, Ting Wang, Hao Chen, Xinying Guan, Chu Zheng, Ping Zeng\",\"doi\":\"10.1016/j.pnpbp.2024.111203\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The gut-microbiome-brain axis (GMBA) implies the connection between inflammatory bowel disease (IBD) and Alzheimer's disease (AD). We aimed to comprehensively explore the relation between IBD (and its subtypes) and AD, early-onset AD (EOAD) and late-onset AD (LOAD) from a genetic pleiotropy perspective.</p><p><strong>Methods: </strong>Relying on summary statistics (N = 472,868 for AD, 185,204 for EOAD, 191,061 for LOAD, 59,957 for IBD, 45,975 for CD, and 40,266 for UC), we first performed Mendelian Randomization to examine the causal association between IBD and AD by leveraging vertical pleiotropy. Then, we estimated global and local genetic correlations, followed by cross-trait association analysis to identify SNPs and genes with horizontal pleiotropy. Particularly, we utilized multi-trait colocalization analysis to assess the role of microbes in the common genetic etiology underlying the two types of diseases. Finally, we conducted functional enrichment analysis for pleiotropic genes.</p><p><strong>Results: </strong>We discovered suggestively causal relations between IBD (and its subtypes) and EOAD (OR<sub>IBD</sub> = 1.06 [1.01-1.11], OR<sub>CD</sub> = 1.05 [1.01-1.10], OR<sub>UC</sub> = 1.08 [1.01-1.15]) as well as between UC and LOAD (OR = 1.04 [1.01-1.08]), and discovered 44 local regions showing suggestively significant genetic correlations between IBD (and its subtypes) and AD (and EODA and LOAD). We further detected substantial genetic overlap, as characterized by 182 CE-associated, 3 EOAD-associated and 51 LOAD-associated pleiotropic SNPs as well as 291 pleiotropic genes. Pleiotropic genes more likely enriched in the GMBA-relevant tissues such as brain, intestine and esophagus. Moreover, we identified three microorganisms related to these disease pairs, including the Catenibacterium, Clostridia, and Prevotella species.</p><p><strong>Conclusion: </strong>The suggestively causal associations and shared genetic basis between IBD and its subtypes with AD, EOAD and LOAD may commonly drive their co-occurrence, and gut microbes might partly explain the shared genetic etiology. Further studies are warranted to elaborate the possibly biological mechanisms underlying the two types of diseases.</p>\",\"PeriodicalId\":54549,\"journal\":{\"name\":\"Progress in Neuro-Psychopharmacology & Biological Psychiatry\",\"volume\":\" \",\"pages\":\"111203\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-11-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Progress in Neuro-Psychopharmacology & Biological Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.pnpbp.2024.111203\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.pnpbp.2024.111203","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Mendelian randomization and genetic pleiotropy analysis for the connection between inflammatory bowel disease and Alzheimer's disease.
Background: The gut-microbiome-brain axis (GMBA) implies the connection between inflammatory bowel disease (IBD) and Alzheimer's disease (AD). We aimed to comprehensively explore the relation between IBD (and its subtypes) and AD, early-onset AD (EOAD) and late-onset AD (LOAD) from a genetic pleiotropy perspective.
Methods: Relying on summary statistics (N = 472,868 for AD, 185,204 for EOAD, 191,061 for LOAD, 59,957 for IBD, 45,975 for CD, and 40,266 for UC), we first performed Mendelian Randomization to examine the causal association between IBD and AD by leveraging vertical pleiotropy. Then, we estimated global and local genetic correlations, followed by cross-trait association analysis to identify SNPs and genes with horizontal pleiotropy. Particularly, we utilized multi-trait colocalization analysis to assess the role of microbes in the common genetic etiology underlying the two types of diseases. Finally, we conducted functional enrichment analysis for pleiotropic genes.
Results: We discovered suggestively causal relations between IBD (and its subtypes) and EOAD (ORIBD = 1.06 [1.01-1.11], ORCD = 1.05 [1.01-1.10], ORUC = 1.08 [1.01-1.15]) as well as between UC and LOAD (OR = 1.04 [1.01-1.08]), and discovered 44 local regions showing suggestively significant genetic correlations between IBD (and its subtypes) and AD (and EODA and LOAD). We further detected substantial genetic overlap, as characterized by 182 CE-associated, 3 EOAD-associated and 51 LOAD-associated pleiotropic SNPs as well as 291 pleiotropic genes. Pleiotropic genes more likely enriched in the GMBA-relevant tissues such as brain, intestine and esophagus. Moreover, we identified three microorganisms related to these disease pairs, including the Catenibacterium, Clostridia, and Prevotella species.
Conclusion: The suggestively causal associations and shared genetic basis between IBD and its subtypes with AD, EOAD and LOAD may commonly drive their co-occurrence, and gut microbes might partly explain the shared genetic etiology. Further studies are warranted to elaborate the possibly biological mechanisms underlying the two types of diseases.
期刊介绍：
Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject.
Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.
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