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Replicated genetic evidence supports a role for HOMER2 in schizophrenia

journal contribution
posted on 2023-06-08, 12:19 authored by William P Gilks, Emma H Allott, Gary Donohoe, Elizabeth Cummings, International Schizophrenia Consortium, Michael Gill, Aiden P Corvin, Derek W Morris
Schizophrenia is a heritable mental disorder with a complex genetic aetiology potentially implicating glutamatergic dysfunction. Following a search for functionally relevant genes with evidence of linkage to schizophrenia, we selected HOMER2 for as a candidate gene for investigation using a multi-stage association design. Twenty-six tagging SNPs were genotyped in 401 cases and 812 controls and associated SNPs were analysed in an independent sample of 408 cases and 804 controls, all from Ireland. Secondary replication analysis was undertaken using the International Schizophrenia Consortium (ISC) European sample of 1287 cases and 1128 controls. Significant associations were found at five SNPs in the first Irish sample (p < 0.05), but were not replicated in the second Irish sample. SNP rs2306428 was significantly associated when the two samples were combined (p = 0.008, OR = 0.73) and also by proxy in the ISC sample (rs17158184, r2 = 1.0, p = 0.019, OR = 0.75). The protective allele at rs2306428 removes a predicted splice-enhancer binding site where Homer2 is naturally truncated. We did not detect an allelic effect of rs2306428 on neuropsychological function nor on HOMER2 splicing. This study supports a role for HOMER2 gene in schizophrenia susceptibility. Further work is required to confirm and elucidate the role of HOMER2 and interacting genes in schizophrenia aetiology.

History

Publication status

  • Published

Journal

Neuroscience letters

ISSN

1872-7972

Publisher

Elsevier

Issue

3

Volume

468

Page range

229-233

Department affiliated with

  • Evolution, Behaviour and Environment Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-09-25

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