RT Journal Article
SR Electronic
T1 Pathways analyses of schizophrenia GWAS focusing on known and novel drug targets
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 091264
DO 10.1101/091264
A1 H. A. Gaspar
A1 G. Breen
YR 2016
UL http://biorxiv.org/content/early/2016/12/02/091264.abstract
AB Schizophrenia is a common, heritable and highly complex psychiatric disorder for which genomewide association studies (GWASs) have discovered >100 loci1. This, and the progress being made in other complex disorders, leads to the questions of how efficiently GWAS can be used to identify novel drug targets and druggable pathways2–4. Taking a series of increasingly better powered GWASs for schizophrenia, we analyse genetic data using information about drug targets and drug therapeutical classes to assess the potential utility of GWAS for drug discovery. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, psycholeptics, and antiepileptics. Drugs targeting calcium channels or nicotinic acetylcholine receptors also show significant association. We conclude that current schizophrenia GWAS results may hold potential therapeutic leads given their power to detect existing treatments. This is a proof of principle study and, given GWAS results of any complex disorder with a sufficient sample size, this approach may be used both to validate the ability of a GWAS to detect known treatments and to identify new drug targets and therapeutic drug families.