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Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross\u2010phenotype genome\u2010wide association study (GWAS) meta\u2010analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed cross\u2010phenotype GWAS meta\u2010analysis and Bayesian colocalization analysis for patients with SSc and patients with PBC. We performed both genome\u2010wide and locus\u2010based analysis, including tissue and pathway enrichment analyses, fine\u2010mapping, Bayesian colocalization analyses with expression quantitative trait loci and protein quantitative trait loci (pQTL) datasets, and phenome\u2010wide association studies. Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We detected a strong genetic correlation between SSc and PBC (global genetic correlation = 0.84,\n                      <jats:italic>P<\/jats:italic>\n                      = 1.7 \u00d7 10\n                      <jats:sup>\u22126<\/jats:sup>\n                      ). In the cross\u2010phenotype GWAS meta\u2010analysis, we identified 44 nonhuman leukocyte antigens loci that reached genome\u2010wide significance (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 5 \u00d7 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). Evidence of shared causal variants between patients with SSc and patients with PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized\n                      <jats:italic>CD40<\/jats:italic>\n                      ,\n                      <jats:italic>ERAP1<\/jats:italic>\n                      ,\n                      <jats:italic>PLD4<\/jats:italic>\n                      ,\n                      <jats:italic>SPPL3<\/jats:italic>\n                      , and\n                      <jats:italic>CCDC113<\/jats:italic>\n                      as novel candidate causal genes. The\n                      <jats:italic>CD40<\/jats:italic>\n                      risk locus colocalized with trans\u2010pQTLs of multiple plasma proteins involved in B cell function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study supports a strong shared genetic susceptibility between SSc and PBC. Using cross\u2010phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43081","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T05:30:02Z","timestamp":1734327002000},"page":"727-739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cross\u2010Phenotype Genome\u2010Wide Association Study on the Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis"],"prefix":"10.1002","volume":"77","author":[{"given":"Yiming","family":"Luo","sequence":"first","affiliation":[{"name":"Columbia University Irving Medical Center  New York City New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atlas","family":"Khan","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center  New York City New 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