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We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene\n                    <jats:italic>DRD2<\/jats:italic>\n                    co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total\n                    <jats:italic>N<\/jats:italic>\n                    =249), we identified a\n                    <jats:italic>DRD2<\/jats:italic>\n                    co-expression pathway enriched for SCZ risk genes. Next, we identified non-coding single-nucleotide polymorphisms (SNPs) associated with co-expression of this pathway. These SNPs were associated with regulatory genetic loci in the dorsolateral prefrontal cortex (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). We summarized their compound effect on co-expression into a Polygenic Co-expression Index (PCI), which predicted\n                    <jats:italic>DRD2<\/jats:italic>\n                    pathway co-expression in both mRNA data sets (all\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). We associated the PCI with brain activity during WM performance in two independent samples of healthy individuals (total\n                    <jats:italic>N<\/jats:italic>\n                    =368) and 29 patients with SCZ who performed the n-back task. Greater predicted\n                    <jats:italic>DRD2<\/jats:italic>\n                    pathway prefrontal co-expression was associated with greater prefrontal activity and longer WM reaction times (all corrected\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05), thus indicating inefficient WM processing. Blind prediction of treatment response to antipsychotics in two independent samples of patients with SCZ suggested better clinical course of patientswith greater PCI (total\n                    <jats:italic>N<\/jats:italic>\n                    =87;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). The findings on this\n                    <jats:italic>DRD2<\/jats:italic>\n                    co-expression pathway are a proof of concept that gene co-expression can parse SCZ risk genes into biological pathways associated with intermediate phenotypes as well as with clinically meaningful information.\n                  <\/jats:p>","DOI":"10.1038\/tp.2016.253","type":"journal-article","created":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T12:29:51Z","timestamp":1484656191000},"page":"e1006-e1006","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia"],"prefix":"10.1038","volume":"7","author":[{"given":"G","family":"Pergola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Di Carlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"D'Ambrosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Gelao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Fazio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Papalino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Monda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Scozia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Pietrangelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Attrotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Apud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V S","family":"Mattay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Rampino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Caforio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D R","family":"Weinberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Blasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Bertolino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,17]]},"reference":[{"key":"BFtp2016253_CR1","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1038\/mp.2013.50","volume":"18","author":"KS Kendler","year":"2013","unstructured":"Kendler KS . 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