{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T15:31:06Z","timestamp":1774625466273,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC2003500"],"award-info":[{"award-number":["2020YFC2003500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["71804093"],"award-info":[{"award-number":["71804093"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009108","name":"Shandong University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Little is known about the genetic basis of clozapine\u2010related neutropaenia. This study aims to explore candidate genes and pathways involved in clozapine\u2010related neutropaenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study conducted a two\u2010stage integrative analysis of the summary statistics from the genome\u2010wide association study (GWAS, <jats:italic>n<\/jats:italic>\u2009=\u2009552) of the lowest absolute neutrophil count (ANC) during clozapine treatment and the summary data of the expressed quantitative trait locus (eQTL). First, we use the probabilistic Mendelian randomization (PMR\u2010Egger) to identify genes whose expression is causally related to ANC, and then use Bayesian co\u2010localization analysis to investigate whether there are shared causal variants between them [posterior probability for hypotheses 4 (PP.H4)\u2009&gt;\u20090.80]. Finally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to explore the pathways that may be associated with ANC during clozapine treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PMR\u2010Egger analysis identified 146 genes that may be causally associated with ANC after Bonferroni correction (<jats:italic>P<\/jats:italic>\u2010value &lt; 3.25e\u20106). Bayesian co\u2010localization analysis identified six further genes whose gene expression shared common variants with ANC, including NT5E (PP.H4\u2009=\u20090.96), GLDC (PP.H4\u2009=\u20090.82), NUDT17 (PP.H4\u2009=\u20090.88), MSH4 (PP.H4\u2009=\u20090.88), PTER (PP.H4\u2009=\u20090.89) and SERPINB6 (PP.H4\u2009=\u20090.83). Enrichment analysis identified 52 GO terms and seven pathways associated with ANC, such as NAD metabolic process, drug catabolic process and glyoxylate and dicarboxylate metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identified multiple candidate genes and pathways that may be involved in clozapine\u2010related neutropaenia, providing novel clues for the mechanism of clozapine\u2010related neutropaenia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15043","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T05:01:00Z","timestamp":1629349260000},"page":"1904-1912","source":"Crossref","is-referenced-by-count":3,"title":["Integration analysis of GWAS and expression quantitative trait loci to identify candidate genes and pathways for clozapine\u2010related 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