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Here, we analyse several genome-wide association studies (GWAS) summary statistics (N\u2009=\u200934,652\u2013456,327), to assess the relationship of AD with GIT disorders. Findings reveal a positive significant genetic overlap and correlation between AD and gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis-duodenitis, irritable bowel syndrome and diverticulosis, but not inflammatory bowel disease. Cross-trait meta-analysis identifies several loci (P\n                    <jats:sub>meta-analysis<\/jats:sub>\n                    \u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) shared by AD and GIT disorders (GERD and PUD) including\n                    <jats:italic>PDE4B<\/jats:italic>\n                    ,\n                    <jats:italic>BRINP3<\/jats:italic>\n                    ,\n                    <jats:italic>ATG16L1<\/jats:italic>\n                    ,\n                    <jats:italic>SEMA3F<\/jats:italic>\n                    ,\n                    <jats:italic>HLA-DRA<\/jats:italic>\n                    ,\n                    <jats:italic>SCARA3<\/jats:italic>\n                    ,\n                    <jats:italic>MTSS2<\/jats:italic>\n                    ,\n                    <jats:italic>PHB<\/jats:italic>\n                    , and\n                    <jats:italic>TOMM40<\/jats:italic>\n                    . Colocalization and gene-based analyses reinforce these loci. Pathway-based analyses demonstrate significant enrichment of lipid metabolism, autoimmunity, lipase inhibitors, PD-1 signalling, and statin mechanisms, among others, for AD and GIT traits. Our findings provide genetic insights into the gut-brain relationship, implicating shared but non-causal genetic susceptibility of GIT disorders with AD\u2019s risk. Genes and biological pathways identified are potential targets for further investigation in AD, GIT disorders, and their comorbidity.\n                  <\/jats:p>","DOI":"10.1038\/s42003-022-03607-2","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T06:16:52Z","timestamp":1658125012000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer\u2019s disease and gastrointestinal tract disorders"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4533-0340","authenticated-orcid":false,"given":"Emmanuel O.","family":"Adewuyi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-7340","authenticated-orcid":false,"given":"Eleanor K.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-3040","authenticated-orcid":false,"given":"Dale R.","family":"Nyholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tenielle","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4355-7082","authenticated-orcid":false,"given":"Simon M.","family":"Laws","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"3607_CR1","unstructured":"Prince, M. 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