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Unravelling the genetic basis of schizophrenia and bipolar disorder with GWAS: A systematic review

Research output: Contribution to journalReview article

Diana P. Prata, Bernardo Costa-neves, Gonçalo Cosme, Evangelos Vassos

Original languageEnglish
Pages (from-to)178-207
Number of pages30
JournalJournal of psychiatric research
Volume114
Early online date12 Apr 2019
DOIs
Publication statusPublished - 1 Jul 2019

King's Authors

Abstract

Objectives
To systematically review findings of GWAS in schizophrenia (SZ) and in bipolar disorder (BD); and to interpret findings, with a focus on identifying independent replications.

Method
PubMed search, selection and review of all independent GWAS in SZ or BD, published since March 2011, i.e. studies using non-overlapping samples within each article, between articles, and with those of the previous review (Li et al., 2012).

Results
From the 22 GWAS included in this review, the genetic associations surviving standard GWAS-significance were for genetic markers in the regions of ACSL3/KCNE4, ADCY2, AMBRA1, ANK3, BRP44, DTL, FBLN1, HHAT, INTS7, LOC392301, LOC645434/NMBR, LOC729457, LRRFIP1, LSM1, MDM1, MHC, MIR2113/POU3F2, NDST3, NKAPL, ODZ4, PGBD1, RENBP, TRANK1, TSPAN18, TWIST2, UGT1A1/HJURP, WHSC1L1/FGFR1 and ZKSCAN4. All genes implicated across both reviews are discussed in terms of their function and implication in neuropsychiatry.

Conclusion
Taking all GWAS to date into account, AMBRA1, ANK3, ARNTL, CDH13, EFHD1 (albeit with different alleles), MHC, PLXNA2 and UGT1A1 have been implicated in either disorder in at least two reportedly non-overlapping samples. Additionally, evidence for a SZ/BD common genetic basis is most strongly supported by the implication of ANK3, NDST3, and PLXNA2.

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