Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26

McAuley, Erica Z., Scimone, Anna, Tiwari, Yash, Agahi, Giti, Mowry, Bryan J., Holliday, Elizabeth G., Donald, Jennifer A., Weickert, Cynthia Shannon, Mitchell, Phillip B., Schofield, Peter R. and Fullerton, Janice M. (2012) Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26. Plos One, 7 5: e38172.1-e38172.10. doi:10.1371/journal.pone.0038172


Author McAuley, Erica Z.
Scimone, Anna
Tiwari, Yash
Agahi, Giti
Mowry, Bryan J.
Holliday, Elizabeth G.
Donald, Jennifer A.
Weickert, Cynthia Shannon
Mitchell, Phillip B.
Schofield, Peter R.
Fullerton, Janice M.
Title Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-05-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0038172
Open Access Status DOI
Volume 7
Issue 5
Start page e38172.1
End page e38172.10
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Plos One
Collection year 2013
Language eng
Formatted abstract
We previously identified a significant bipolar spectrum disorder linkage peak on 15q25-26 using 35 extended families with a broad clinical phenotype, including bipolar disorder (types I and II), recurrent unipolar depression and schizoaffective disorder. However, the specific gene(s) contributing to this signal had not been identified. By a fine mapping association study in an Australian case-control cohort (n = 385), we find that the sialyltransferase 8B (ST8SIA2) gene, coding for an enzyme that glycosylates proteins involved in neuronal plasticity which has previously shown association to both schizophrenia and autism, is associated with increased risk to bipolar spectrum disorder. Nominal single point association was observed with SNPs in ST8SIA2 (rs4586379, P = 0.0043; rs2168351, P = 0.0045), and a specific risk haplotype was identified (frequency: bipolar vs controls = 0.41 vs 0.31; χ 2 = 6.46, P = 0.011, OR = 1.47). Over-representation of the specific risk haplotype was also observed in an Australian schizophrenia case-control cohort (n = 256) (χ 2 = 8.41, P = 0.004, OR = 1.82). Using GWAS data from the NIMH bipolar disorder (n = 2055) and NIMH schizophrenia (n = 2550) cohorts, the equivalent haplotype was significantly over-represented in bipolar disorder (χ 2 = 5.91, P = 0.015, OR = 1.29), with the same direction of effect in schizophrenia, albeit non-significant (χ 2 = 2.3, P = 0.129, OR = 1.09). We demonstrate marked down-regulation of ST8SIA2 gene expression across human brain development and show a significant haplotype×diagnosis effect on ST8SIA2 mRNA levels in adult cortex (ANOVA: F(1,87) = 6.031, P = 0.016). These findings suggest that variation the ST8SIA2 gene is associated with increased risk to mental illness, acting to restrict neuronal plasticity and disrupt early neuronal network formation, rendering the developing and adult brain more vulnerable to secondary genetic or environmental insults.
Keyword Cell-adhesion molecule
Bipolar affective-disorder
Genome-wide scan
Polysialic acid
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2013 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 22 Nov 2012, 22:23:31 EST by Debra McMurtrie on behalf of Queensland Brain Institute