Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis
Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively ass...
| Main Authors: | , , , |
|---|---|
| Format: | Journal Article |
| Language: | English |
| Published: |
MDPI
2022
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/97667 |
| _version_ | 1848766300490301440 |
|---|---|
| author | Adewuyi, Emmanuel O’Brien, E.K. Porter, T. Laws, S.M. |
| author_facet | Adewuyi, Emmanuel O’Brien, E.K. Porter, T. Laws, S.M. |
| author_sort | Adewuyi, Emmanuel |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with several GIT disorders. We demonstrate a strong and highly significant inverse global genetic correlation between cognitive traits and GIT disorders—peptic ulcer disease (PUD), gastritis-duodenitis, diverticulosis, irritable bowel syndrome, and gastroesophageal reflux disease (GERD), but not inflammatory bowel disease (IBD). Further analysis detects 35 significant (p < 4.37 × 10−5) bivariate local genetic correlations between cognitive traits, AD, and GIT disorders (including IBD). Mendelian randomisation analysis suggests a risk-decreasing causality of educational attainment, intelligence, and other cognitive traits on PUD and GERD, but not IBD, and a putative association of GERD with cognitive function decline. Gene-based analysis reveals a significant gene-level genetic overlap of cognitive traits with AD and GIT disorders (IBD inclusive, pbinomial-test = 1.18 × 10−3–2.20 × 10−16). Our study supports the protective roles of genetically-influenced educational attainments and other cognitive traits on the risk of GIT disorders and highlights a putative association of GERD with cognitive function decline. Findings from local genetic correlation analysis provide novel insights, indicating that the relationship of IBD with cognitive traits (and AD) will depend largely on their local effects across the genome. |
| first_indexed | 2025-11-14T11:48:57Z |
| format | Journal Article |
| id | curtin-20.500.11937-97667 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:48:57Z |
| publishDate | 2022 |
| publisher | MDPI |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-976672025-05-03T08:15:04Z Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis Adewuyi, Emmanuel O’Brien, E.K. Porter, T. Laws, S.M. Science & Technology Life Sciences & Biomedicine Physical Sciences Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry Alzheimer's disease causality cognition cognitive traits educational attainment gastrointestinal tract disorders genome-wide association studies (GWAS) local genetic correlation global genetic correlation Mendelian randomization ASSOCIATION IMPAIRMENT MICROBIOTA Alzheimer’s disease Mendelian randomization causality cognition cognitive traits educational attainment gastrointestinal tract disorders genome-wide association studies (GWAS) global genetic correlation local genetic correlation Humans Alzheimer Disease Genome-Wide Association Study Cognition Gastroesophageal Reflux Inflammatory Bowel Diseases Polymorphism, Single Nucleotide Humans Gastroesophageal Reflux Inflammatory Bowel Diseases Alzheimer Disease Cognition Polymorphism, Single Nucleotide Genome-Wide Association Study Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with several GIT disorders. We demonstrate a strong and highly significant inverse global genetic correlation between cognitive traits and GIT disorders—peptic ulcer disease (PUD), gastritis-duodenitis, diverticulosis, irritable bowel syndrome, and gastroesophageal reflux disease (GERD), but not inflammatory bowel disease (IBD). Further analysis detects 35 significant (p < 4.37 × 10−5) bivariate local genetic correlations between cognitive traits, AD, and GIT disorders (including IBD). Mendelian randomisation analysis suggests a risk-decreasing causality of educational attainment, intelligence, and other cognitive traits on PUD and GERD, but not IBD, and a putative association of GERD with cognitive function decline. Gene-based analysis reveals a significant gene-level genetic overlap of cognitive traits with AD and GIT disorders (IBD inclusive, pbinomial-test = 1.18 × 10−3–2.20 × 10−16). Our study supports the protective roles of genetically-influenced educational attainments and other cognitive traits on the risk of GIT disorders and highlights a putative association of GERD with cognitive function decline. Findings from local genetic correlation analysis provide novel insights, indicating that the relationship of IBD with cognitive traits (and AD) will depend largely on their local effects across the genome. 2022 Journal Article http://hdl.handle.net/20.500.11937/97667 10.3390/ijms232416199 English MDPI unknown |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Physical Sciences Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry Alzheimer's disease causality cognition cognitive traits educational attainment gastrointestinal tract disorders genome-wide association studies (GWAS) local genetic correlation global genetic correlation Mendelian randomization ASSOCIATION IMPAIRMENT MICROBIOTA Alzheimer’s disease Mendelian randomization causality cognition cognitive traits educational attainment gastrointestinal tract disorders genome-wide association studies (GWAS) global genetic correlation local genetic correlation Humans Alzheimer Disease Genome-Wide Association Study Cognition Gastroesophageal Reflux Inflammatory Bowel Diseases Polymorphism, Single Nucleotide Humans Gastroesophageal Reflux Inflammatory Bowel Diseases Alzheimer Disease Cognition Polymorphism, Single Nucleotide Genome-Wide Association Study Adewuyi, Emmanuel O’Brien, E.K. Porter, T. Laws, S.M. Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis |
| title | Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis |
| title_full | Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis |
| title_fullStr | Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis |
| title_full_unstemmed | Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis |
| title_short | Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis |
| title_sort | relationship of cognition and alzheimer’s disease with gastrointestinal tract disorders: a large-scale genetic overlap and mendelian randomisation analysis |
| topic | Science & Technology Life Sciences & Biomedicine Physical Sciences Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry Alzheimer's disease causality cognition cognitive traits educational attainment gastrointestinal tract disorders genome-wide association studies (GWAS) local genetic correlation global genetic correlation Mendelian randomization ASSOCIATION IMPAIRMENT MICROBIOTA Alzheimer’s disease Mendelian randomization causality cognition cognitive traits educational attainment gastrointestinal tract disorders genome-wide association studies (GWAS) global genetic correlation local genetic correlation Humans Alzheimer Disease Genome-Wide Association Study Cognition Gastroesophageal Reflux Inflammatory Bowel Diseases Polymorphism, Single Nucleotide Humans Gastroesophageal Reflux Inflammatory Bowel Diseases Alzheimer Disease Cognition Polymorphism, Single Nucleotide Genome-Wide Association Study |
| url | http://hdl.handle.net/20.500.11937/97667 |