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dc.contributor.authorLiu, C
dc.contributor.authorBousman, CA
dc.contributor.authorPantelis, C
dc.contributor.authorSkafidas, E
dc.contributor.authorZhang, D
dc.contributor.authorYue, W
dc.contributor.authorEverall, IP
dc.date.accessioned2020-12-22T05:27:52Z
dc.date.available2020-12-22T05:27:52Z
dc.date.issued2017-02-21
dc.identifierpii: tp20178
dc.identifier.citationLiu, C., Bousman, C. A., Pantelis, C., Skafidas, E., Zhang, D., Yue, W. & Everall, I. P. (2017). Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations. TRANSLATIONAL PSYCHIATRY, 7 (2), https://doi.org/10.1038/tp.2017.8.
dc.identifier.issn2158-3188
dc.identifier.urihttp://hdl.handle.net/11343/258294
dc.description.abstractGenome-wide association studies have confirmed the polygenic nature of schizophrenia and suggest that there are hundreds or thousands of alleles associated with increased liability for the disorder. However, the generalizability of any one allelic marker of liability is remarkably low and has bred the notion that schizophrenia may be better conceptualized as a pathway(s) disorder. Here, we empirically tested this notion by conducting a pathway-wide association study (PWAS) encompassing 255 experimentally validated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways among 5033 individuals diagnosed with schizophrenia and 5332 unrelated healthy controls across three distinct ethnic populations; European-American (EA), African-American (AA) and Han Chinese (CH). We identified 103, 74 and 87 pathways associated with schizophrenia liability in the EA, CH and AA populations, respectively. About half of these pathways were uniquely associated with schizophrenia liability in each of the three populations. Five pathways (serotonergic synapse, ubiquitin mediated proteolysis, hedgehog signaling, adipocytokine signaling and renin secretion) were shared across all three populations and the single-nucleotide polymorphism sets representing these five pathways were enriched for single-nucleotide polymorphisms with regulatory function. Our findings provide empirical support for schizophrenia as a pathway disorder and suggest schizophrenia is not only a polygenic but likely also a poly-pathway disorder characterized by both genetic and pathway heterogeneity.
dc.languageEnglish
dc.publisherSPRINGERNATURE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlePathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations
dc.typeJournal Article
dc.identifier.doi10.1038/tp.2017.8
melbourne.affiliation.departmentElectrical and Electronic Engineering
melbourne.affiliation.departmentPsychiatry
melbourne.source.titleTranslational Psychiatry
melbourne.source.volume7
melbourne.source.issue2
melbourne.identifier.nhmrc628386
melbourne.identifier.nhmrc1105825
dc.rights.licenseCC BY
melbourne.elementsid1191091
melbourne.contributor.authorEverall, Ian
melbourne.contributor.authorBousman, Chad
melbourne.contributor.authorPantelis, Christos
melbourne.contributor.authorSkafidas, Efstratios
melbourne.contributor.authorLiu, Chenxing
dc.identifier.eissn2158-3188
melbourne.identifier.fundernameidNHMRC, 628386
melbourne.identifier.fundernameidNHMRC, 1105825
melbourne.accessrightsOpen Access


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