{"id":"https://openalex.org/W7225339735","doi":"https://doi.org/10.64898/2026.11.03.26367234","title":"Single-Cell Transcriptome-Wide Mendelian Randomization and Colocalization Analysis Reveals Immune Cell-Specific Mechanisms in Alzheimer\u2019s Disease","display_name":"Single-Cell Transcriptome-Wide Mendelian Randomization and Colocalization Analysis Reveals Immune Cell-Specific Mechanisms in Alzheimer\u2019s Disease","publication_year":2026,"publication_date":"2026-11-05","ids":{"openalex":"https://openalex.org/W7225339735","doi":"https://doi.org/10.64898/2026.11.03.26367234"},"language":"en","primary_location":{"id":"doi:10.64898/2026.11.03.26367234","doi":"https://doi.org/10.64898/2026.11.03.26367234","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.03.26367234","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/11/05/2026.11.03.26367234.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.medrxiv.org/content/medrxiv/early/2026/11/05/2026.11.03.26367234.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5077004238","display_name":"Youwei Si","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I38877650","display_name":"Zhengzhou University","ror":"https://ror.org/04ypx8c21","country_code":"CN","type":"education","lineage":["https://openalex.org/I38877650"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Youwei Si","raw_affiliation_strings":["Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China","The First Clinical Medical College of Zhengzhou University, Zhengzhou 420001, Henan, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China","institution_ids":["https://openalex.org/I38877650"]},{"raw_affiliation_string":"The First Clinical Medical College of Zhengzhou University, Zhengzhou 420001, Henan, China","institution_ids":["https://openalex.org/I38877650"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5035168953","display_name":"Youwen Si","orcid":"https://orcid.org/0000-0003-3093-6355","observed_orcids":["https://orcid.org/0000-0003-3093-6355"]},"institutions":[{"id":"https://openalex.org/I38877650","display_name":"Zhengzhou University","ror":"https://ror.org/04ypx8c21","country_code":"CN","type":"education","lineage":["https://openalex.org/I38877650"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Youwen Si","raw_affiliation_strings":["Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China","The First Clinical Medical College of Zhengzhou University, Zhengzhou 420001, Henan, China"],"raw_orcid":"https://orcid.org/0000-0003-3093-6355","affiliations":[{"raw_affiliation_string":"Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China","institution_ids":["https://openalex.org/I38877650"]},{"raw_affiliation_string":"The First Clinical Medical College of Zhengzhou University, Zhengzhou 420001, Henan, China","institution_ids":["https://openalex.org/I38877650"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5035168953"],"corresponding_institution_ids":["https://openalex.org/I38877650"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.6729000210762024,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.6729000210762024,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.24330000579357147,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10009","display_name":"Dementia and Cognitive Impairment Research","score":0.02969999983906746,"subfield":{"id":"https://openalex.org/subfields/2738","display_name":"Psychiatry and Mental health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/alzheimer-s-disease","display_name":"Alzheimer's disease","score":0.9990000128746033},{"id":"https://openalex.org/keywords/mendelian-randomization","display_name":"Mendelian randomization","score":0.8230000138282776},{"id":"https://openalex.org/keywords/bayesian-colocalization","display_name":"Bayesian colocalization","score":0.9470000267028809},{"id":"https://openalex.org/keywords/peripheral-immune-cells","display_name":"peripheral immune cells","score":0.8339999914169312},{"id":"https://openalex.org/keywords/tnf-alpha","display_name":"TNF-\u03b1","score":0.8659999966621399},{"id":"https://openalex.org/keywords/mhc-class-ii-antigen-presentation","display_name":"MHC class II antigen presentation","score":0.9049999713897705},{"id":"https://openalex.org/keywords/phagocytosis","display_name":"phagocytosis","score":0.9459999799728394},{"id":"https://openalex.org/keywords/t-cell-activation","display_name":"T cell activation","score":0.9070000052452087}],"concepts":[{"id":"https://openalex.org/C2779901538","wikidata":"https://www.wikidata.org/wiki/Q6816584","display_name":"Mendelian randomization","level":5,"score":0.7493000030517578},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.73580002784729},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.6399999856948853},{"id":"https://openalex.org/C168393362","wikidata":"https://www.wikidata.org/wiki/Q5421706","display_name":"Expression quantitative trait loci","level":5,"score":0.6255000233650208},{"id":"https://openalex.org/C207936829","wikidata":"https://www.wikidata.org/wiki/Q423163","display_name":"Major histocompatibility complex","level":3,"score":0.6031000018119812},{"id":"https://openalex.org/C106208931","wikidata":"https://www.wikidata.org/wiki/Q1098876","display_name":"Genome-wide association study","level":5,"score":0.5940999984741211},{"id":"https://openalex.org/C69991583","wikidata":"https://www.wikidata.org/wiki/Q1423575","display_name":"Candidate gene","level":3,"score":0.5356000065803528},{"id":"https://openalex.org/C186413461","wikidata":"https://www.wikidata.org/wiki/Q744727","display_name":"Genetic association","level":5,"score":0.5285000205039978},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5206999778747559},{"id":"https://openalex.org/C188280979","wikidata":"https://www.wikidata.org/wiki/Q911125","display_name":"Human leukocyte antigen","level":3,"score":0.49799999594688416},{"id":"https://openalex.org/C35605836","wikidata":"https://www.wikidata.org/wiki/Q2064311","display_name":"Linkage disequilibrium","level":5,"score":0.48919999599456787},{"id":"https://openalex.org/C84597430","wikidata":"https://www.wikidata.org/wiki/Q106227","display_name":"Locus (genetics)","level":3,"score":0.4562999904155731},{"id":"https://openalex.org/C81941488","wikidata":"https://www.wikidata.org/wiki/Q853421","display_name":"Quantitative trait locus","level":3,"score":0.45190000534057617},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.45159998536109924},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.44589999318122864},{"id":"https://openalex.org/C189014844","wikidata":"https://www.wikidata.org/wiki/Q189118","display_name":"Cell type","level":3,"score":0.44190001487731934},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.43380001187324524},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.42489999532699585},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.42399999499320984},{"id":"https://openalex.org/C197754878","wikidata":"https://www.wikidata.org/wiki/Q80711","display_name":"Haplotype","level":4,"score":0.3537999987602234},{"id":"https://openalex.org/C40209533","wikidata":"https://www.wikidata.org/wiki/Q5147828","display_name":"Colocalization","level":2,"score":0.353300005197525},{"id":"https://openalex.org/C175783326","wikidata":"https://www.wikidata.org/wiki/Q185055","display_name":"Mendelian inheritance","level":3,"score":0.33959999680519104},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.31290000677108765},{"id":"https://openalex.org/C142870003","wikidata":"https://www.wikidata.org/wiki/Q843863","display_name":"Genetic linkage","level":3,"score":0.3066999912261963},{"id":"https://openalex.org/C153209595","wikidata":"https://www.wikidata.org/wiki/Q501128","display_name":"Single-nucleotide polymorphism","level":4,"score":0.3034000098705292},{"id":"https://openalex.org/C170627219","wikidata":"https://www.wikidata.org/wiki/Q13218497","display_name":"MHC class I","level":4,"score":0.29280000925064087},{"id":"https://openalex.org/C167672396","wikidata":"https://www.wikidata.org/wiki/Q417800","display_name":"CD8","level":3,"score":0.29260000586509705},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.2802000045776367},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.26109999418258667}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.11.03.26367234","doi":"https://doi.org/10.64898/2026.11.03.26367234","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.03.26367234","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/11/05/2026.11.03.26367234.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.11.03.26367234","doi":"https://doi.org/10.64898/2026.11.03.26367234","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.03.26367234","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/11/05/2026.11.03.26367234.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":1.0}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225339735.pdf","grobid_xml":"https://content.openalex.org/works/W7225339735.grobid-xml"},"referenced_works_count":35,"referenced_works":["https://openalex.org/W1967399741","https://openalex.org/W2035618305","https://openalex.org/W2073836327","https://openalex.org/W2098613848","https://openalex.org/W2112203259","https://openalex.org/W2113699335","https://openalex.org/W2126020723","https://openalex.org/W2143282831","https://openalex.org/W2264585211","https://openalex.org/W2324862792","https://openalex.org/W2328393125","https://openalex.org/W2613603864","https://openalex.org/W2805983714","https://openalex.org/W2901303766","https://openalex.org/W2916749909","https://openalex.org/W3000319248","https://openalex.org/W3123487455","https://openalex.org/W3191451220","https://openalex.org/W3197290161","https://openalex.org/W3202212354","https://openalex.org/W3210570897","https://openalex.org/W4223591189","https://openalex.org/W4223893712","https://openalex.org/W4282024710","https://openalex.org/W4289261763","https://openalex.org/W4296478810","https://openalex.org/W4323832104","https://openalex.org/W4381612968","https://openalex.org/W4402307804","https://openalex.org/W4403761397","https://openalex.org/W4409980681","https://openalex.org/W4412434896","https://openalex.org/W4413108206","https://openalex.org/W4413756367","https://openalex.org/W4416797440"],"related_works":["https://openalex.org/W7140026511","https://openalex.org/W7216193450","https://openalex.org/W4391436959","https://openalex.org/W7165545338","https://openalex.org/W4390606882","https://openalex.org/W4400664786","https://openalex.org/W4392919711","https://openalex.org/W7203713268","https://openalex.org/W4406197112","https://openalex.org/W4412375918"],"abstract_inverted_index":{"Abstract":[0],"Objective":[1],"To":[2],"integrate":[3],"single-cell":[4,56,271],"expression":[5,211,296],"quantitative":[6],"trait":[7],"locus":[8],"(sc-eQTL),":[9],"Alzheimer\u2019s":[10],"disease":[11],"(AD)":[12],"genome-wide":[13,260],"association":[14,108],"study":[15,109,268],"(GWAS),":[16],"and":[17,29,62,85,106,114,194,216,233,255,318],"Bayesian":[18,104],"colocalization":[19,275],"analyses,":[20],"in":[21,38,149,175,182,212,253,291,299,315],"order":[22],"to":[23,280],"systematically":[24],"identify":[25],"candidate":[26,139,228],"causal":[27,140],"genes":[28,145,174,229],"potential":[30],"immune":[31,40,50,153,159,177],"mechanisms":[32,287],"that":[33,157,171,240,270],"specifically":[34],"regulate":[35],"AD":[36,64,135,217,310],"risk":[37,218],"peripheral":[39,48,289],"cells.":[41],"Methods":[42],"Using":[43],"the":[44,54,63,115,172,223,241,246,282],"cis-eQTLs":[45],"of":[46,197,245,288,297],"14":[47],"blood":[49],"cell":[51,154,164,178,199,283],"types":[52,179],"from":[53],"OneK1K":[55],"eQTL":[57],"dataset":[58,117],"as":[59,67],"exposure":[60],"data":[61],"GWAS":[65],"(GCST90565439)":[66],"outcome":[68],"data,":[69],"a":[70,151,204],"two-sample":[71],"Mendelian":[72],"randomization":[73],"(MR)":[74],"analysis":[75,126,169,202,276],"was":[76,118],"performed.":[77],"Weak":[78],"instrumental":[79,248],"variables":[80],"were":[81,90,111,180,250],"removed":[82],"using":[83],"F-statistics,":[84],"approximately":[86],"independent":[87,316],"genetic":[88,160,207,285],"instruments":[89],"obtained":[91],"by":[92],"linkage":[93],"disequilibrium":[94],"pruning.":[95],"For":[96],"significant":[97,147,173,242,261],"gene\u2013cell":[98,129],"type":[99,130,165],"associations,":[100],"compareCluster":[101],"functional":[102,319],"enrichment,":[103],"colocalization,":[105],"phenome-wide":[107],"(PheWAS)":[110],"further":[112,313],"performed,":[113],"1M-scBloodNL":[116,224],"used":[119,279],"for":[120,309],"replication":[121,225],"validation.":[122],"Results":[123],"The":[124,236,293],"MR":[125],"identified":[127],"187":[128],"associations":[131,148,244,264],"significantly":[132],"associated":[133],"with":[134,258,274],"risk,":[136,311],"involving":[137],"161":[138],"genes.":[141],"Among":[142],"them,":[143],"141":[144],"showed":[146,170,230],"only":[150],"single":[152],"type,":[155],"suggesting":[156],"AD-related":[158],"regulation":[161,196],"has":[162],"marked":[163],"specificity.":[166],"Functional":[167],"enrichment":[168],"different":[176],"enriched":[181],"biological":[183],"processes":[184],"including":[185],"MHC":[186],"class":[187],"II":[188],"antigen":[189],"presentation,":[190],"phagocytosis,":[191],"membrane":[192],"invagination,":[193],"positive":[195],"T":[198,214,301],"activation.":[200],"Colocalization":[201],"indicated":[203],"strong":[205],"shared":[206],"signal":[208,308],"between":[209],"TNF":[210,247,298],"CD4+SOX4+":[213,300],"cells":[215,302],"(PP.H4":[219],"=":[220],"0.833).":[221],"In":[222],"analysis,":[226],"several":[227],"consistent":[231],"direction":[232],"nominal":[234],"significance.":[235],"PheWAS":[237],"results":[238],"suggested":[239],"phenotypic":[243,263],"variable":[249],"mainly":[251],"concentrated":[252],"immune-":[254],"hematology-related":[256],"traits,":[257],"no":[259],"neurological":[262],"observed.":[265],"Conclusion":[266],"This":[267],"suggests":[269],"eQTL-MR":[272],"combined":[273],"can":[277],"be":[278],"dissect":[281],"type-specific":[284],"regulatory":[286],"immunity":[290],"AD.":[292],"genetically":[294],"predicted":[295],"may":[303],"represent":[304],"an":[305],"important":[306],"immune-related":[307],"but":[312],"validation":[314],"populations":[317],"experiments":[320],"is":[321],"still":[322],"required.":[323]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-06T00:00:00"}