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Seventy pleiotropic single\u2010nucleotide polymorphisms (SNPs) shared between AD and 11 immune disorders were analyzed. AlphaGenome assessed functional regulation, and The Alzheimer's Cell Atlas (TACA) database was used for drug\u2010target relevance of\n                      <jats:italic>FCER1G<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Across 54 Genotype\u2010Tissue Expression (GTEx) tissues, 410 SNP\u2013gene\u2013tissue co\u2010localizations were identified. SNP rs4233366 co\u2010localized with eQTL\/meQTL signals at\n                      <jats:italic>FCER1G<\/jats:italic>\n                      , whereas\n                      <jats:italic>TSPAN14<\/jats:italic>\n                      ,\n                      <jats:italic>ISYNA1<\/jats:italic>\n                      , and\n                      <jats:italic>ELL<\/jats:italic>\n                      showed splicing and single\u2010cell associations. Mendelian randomization and mediation analyses indicated cytosine\u2010phosphate\u2010Guanine (CpG) sites might effect on AD risk mediated through\n                      <jats:italic>FCER1G<\/jats:italic>\n                      . AlphaGenome and TACA validated\n                      <jats:italic>FCER1G\u2019<\/jats:italic>\n                      s the regulatory function and therapeutic relevance of\n                      <jats:italic>FCER1G<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>PRISM\u2010xQTL refines causal inference for noncoding risk variants, highlighting immune regulatory mechanisms and prioritizing therapeutic targets in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>We developed PRISM\u2010xQTL (Pleiotropic Relationships Integrated with System\u2010level Multiomic QTL), a multiomic framework integrating pleiotropy, co\u2010localization, Mendelian randomization, and mediation analyses to dissect genetic regulation in Alzheimer's disease (AD) and immune\u2010mediated diseases.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Identified 410 single\u2010nucleotide polymorphism (SNP)\u2013gene\u2013tissue co\u2010localizations across 54 Genotype\u2010Tissue Expression (GTEx) tissues, including 28 multi\u2010gene\/multi\u2010tissue signals, 35 methylation quantitative trait locus (meQTL) pairs in blood, with rs4233366 and rs479486 overlapping expression QTLs (eQTLs).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Multi\u2010trait co\u2010localization, Mendelian randomization and mediation analyses at rs4233366 and rs479486 revealed convergent regulatory effects across genes and tissues.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            AlphaGenome profiling showed that rs4233366 drives allele\u2010specific transcriptional and splicing regulation at\n                            <jats:italic>FCER1G<\/jats:italic>\n                            , linking immune signaling to AD risk.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71073","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T03:28:33Z","timestamp":1769743713000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PRISM\u2010xQTL: Pleiotropic Relationships Integrated with System\u2010level Multiomic QTL analysis for causal genes and 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