Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach.
Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach.
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DOI：
10.1038/s41598-017-12325-3
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发表时间：
2017-09-29
影响因子：
4.6
通讯作者：
Breen G
中科院分区：
文献类型：
--
作者：
Gaspar HA;Breen G
Using successful genome-wide association results in psychiatry for drug repurposing is an ongoing challenge. Databases collecting drug targets and gene annotations are growing and can be harnessed to shed a new light on psychiatric disorders. We used genome-wide association study (GWAS) summary statistics from the Psychiatric Genetics Consortium (PGC) Schizophrenia working group to build a drug repositioning model for schizophrenia. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, selective calcium channel blockers, and antiepileptics. Each of these therapeutical classes targets different gene subnetworks. We identify 123 Bonferroni-significant druggable genes outside the MHC, and 128 FDR-significant biological pathways related to neurons, synapses, genic intolerance, membrane transport, epilepsy, and mental disorders. These results suggest that, in schizophrenia, current well-powered GWAS results can reliably detect known schizophrenia drugs and thus may hold considerable potential for the identification of new therapeutic leads. Moreover, antiepileptics and calcium channel blockers may provide repurposing opportunities. This study also reveals significant pathways in schizophrenia that were not identified previously, and provides a workflow for pathway analysis and drug repurposing using GWAS results.
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影响因子：
25
作者：
Breen G;Li Q;Roth BL;O'Donnell P;Didriksen M;Dolmetsch R;O'Reilly PF;Gaspar HA;Manji H;Huebel C;Kelsoe JR;Malhotra D;Bertolino A;Posthuma D;Sklar P;Kapur S;Sullivan PF;Collier DA;Edenberg HJ
通讯作者：
Edenberg HJ
影响因子：
3.7
作者：
Imbrici P;Camerino DC;Tricarico D
通讯作者：
Tricarico D
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
17.1
作者：
Finan C;Gaulton A;Kruger FA;Lumbers RT;Shah T;Engmann J;Galver L;Kelley R;Karlsson A;Santos R;Overington JP;Hingorani AD;Casas JP
通讯作者：
Casas JP
影响因子：
2.9
作者：
Bishop, CM;Svensen, M;Williams, CKI
通讯作者：
Williams, CKI