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Genetic factors are likely to play a role in the molecular basis of CIA. We explored an in vitro system to study the genetic susceptibility of CIA. Cell viability was measured in 90 lymphoblast cell lines exposed to a series of increasing concentrations of clozapine for 48\u2009hr. Quantitative trait measures of cell viability as well as area under the survival curve were used in a linear mixed model for genome\u2010wide association analyses. The estimated heritability of clozapine\u2010induced cell viability reduction in these cell lines is h<jats:sup>2<\/jats:sup>\u2009=\u20090.76. No genome\u2010wide significant association was observed after correction for multiple testing. Two independent loci with nominal evidence of association were observed at 30\u00d7 clinical clozapine concentration: rs2709505 (<jats:italic>P<\/jats:italic>\u2009=\u20091.41\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) in an intron of<jats:italic>MDFIC<\/jats:italic>and rs10457252 (<jats:italic>P<\/jats:italic>\u2009=\u20091.79\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) located in a gene desert at chromosome 6q21. We identified one locus (rs1293970) near<jats:italic>PRG4<\/jats:italic>that was consistently associated for all separate concentration analyses at<jats:italic>P<\/jats:italic>\u2009&lt;\u20095\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>.<jats:italic>PRG4<\/jats:italic>encodes hemangiopoietin, a growth stimulator for hematopoietic stem cells. No evidence was observed for involvement of the MHC region. Our results demonstrate that clozapine\u2010induced viability reduction in lymphoblast cell lines is a heritable, polygenic trait. Thus, in vitro models of CIA might be a useful tool for future discovery of genetic risk factors, although larger sample sizes will be required to unambiguously identify these loci. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32287","type":"journal-article","created":{"date-parts":[[2015,2,6]],"date-time":"2015-02-06T04:05:46Z","timestamp":1423195546000},"page":"116-122","source":"Crossref","is-referenced-by-count":6,"title":["Genome\u2010wide association study of lymphoblast cell viability after clozapine exposure"],"prefix":"10.1002","volume":"168","author":[{"given":"S.A.J.","family":"de With","sequence":"first","affiliation":[{"name":"UCLA Center for Neurobehavioral Genetics Semel Institute for Neuroscience and Human Behavior University of California Los Angeles California"},{"name":"Brain Center Rudolf Magnus Department of Psychiatry University Medical Center Utrecht The 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