Wnt receptor gene FZD1 was associated with schizophrenia in genome-wide SNP analysis of the Australian Schizophrenia Research Bank cohort

Xiaoman Liu, Siew Kee Low, Joshua R. Atkins, Jing Qin Wu, William R. Reay, Heath M. Cairns, Melissa J. Green, Ulrich Schall, Assen Jablensky, Bryan Mowry, Patricia T. Michie, Stan V. Catts, Frans Henskens, Christos Pantelis, Carmel Loughland, Alan V. Boddy, Paul A. Tooney, Rodney J. Scott, Vaughan J. Carr, Murray J. Cairns

Research output: Contribution to journalArticlepeer-review

5 Citations (Web of Science)

Abstract

Objectives: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to understanding this complex but highly heritable psychotic disorder. To further investigate loci, genes and pathways associated more specifically in the well-characterized Australian Schizophrenia Research Bank cohort, we applied genome-wide single-nucleotide polymorphism analysis in these three annotation categories. Methods: We performed a case–control genome-wide association study in 429 schizophrenia samples and 255 controls. Post-genome-wide association study analyses were then integrated with genomic annotations to explore the enrichment of variation at the gene and pathway level. We also examine candidate single-nucleotide polymorphisms with potential function within expression quantitative trait loci and investigate overall enrichment of variation within tissue-specific functional regulatory domains of the genome. Results: The strongest finding (p = 2.01 × 10−6, odds ratio = 1.82, 95% confidence interval = [1.42, 2.33]) in genome-wide association study was with rs10252923 at 7q21.13, downstream of FZD1 (frizzled class receptor 1). While this did not stand alone after correction, the involvement of FZD1 was supported by gene-based analysis, which exceeded the threshold for genome-wide significance (p = 2.78 × 10−6). Conclusion: The identification of FZD1, as an independent association signal at the gene level, supports the hypothesis that the Wnt signalling pathway is altered in the pathogenesis of schizophrenia and may be an important target for therapeutic development.

Original languageEnglish
Pages (from-to)902-908
Number of pages7
JournalAustralian and New Zealand Journal of Psychiatry
Volume54
Issue number9
DOIs
Publication statusPublished - Sep 2020

Fingerprint

Dive into the research topics of 'Wnt receptor gene FZD1 was associated with schizophrenia in genome-wide SNP analysis of the Australian Schizophrenia Research Bank cohort'. Together they form a unique fingerprint.

Cite this