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Association between ST8SIA2 and the Risk of Schizophrenia and Bipolar I Disorder across Diagnostic Boundaries.

Yang SY, Huh IS, Baek JH, Cho EY, Choi MJ, Ryu S, Kim JS, Park T, Ha K, Hong KS - PLoS ONE (2015)

Bottom Line: Thirty-one tag single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing significant associations in previous studies were genotyped.Fourteen of 34 SNPs showed a nominally significant association (p < 0.05) with at least one diagnostic group.Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.

ABSTRACT

Background: Findings from family studies and recent genome-wide association studies have indicated overlap in the risk genes between schizophrenia and bipolar disorder (BD). After finding a linkage between the ST8SIA2 (ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sicalyltransferase 2 gene) locus (15q26) and mixed families with schizophrenia and BD, several studies have reported a significant association between this gene and schizophrenia or BD. We investigated the genetic association between ST8SIA2 and both schizophrenia and BD in the Korean population.

Methods: A total of 582 patients with schizophrenia, 339 patients with BD, and 502 healthy controls were included. Thirty-one tag single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing significant associations in previous studies were genotyped. The associations were evaluated by logistic regression analysis using additive, dominant, and recessive genetic models.

Results: Fourteen of 34 SNPs showed a nominally significant association (p < 0.05) with at least one diagnostic group. These association trends were strongest for the schizophrenia and combined schizophrenia and bipolar I disorder (BD-I) groups. The strongest association was observed in rs11637898 for schizophrenia (p = 0.0033) and BD-I (p = 0.0050) under the dominant model. The association between rs11637898 and the combined schizophrenia and BD-I group (p = 0.0006, under the dominant model) remained significant after correcting for multiple testing.

Discussion: We identified a possible role of ST8SIA2 in the common susceptibility of schizophrenia and BD-I. However, no association trend was observed for bipolar II disorder. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

No MeSH data available.


Related in: MedlinePlus

Relative positions of the ST8SIA2 single nucleotide polymorphisms (SNPs) analyzed in the current study and previous studies reporting positive associations with schizophrenia or bipolar disorder.BD-I, bipolar I disorder; BD, bipolar disorder. Relative positions of the exons are displayed in the left column. Colored area is the covered area of the gene in the corresponding study. Box with bold outline indicates high linkage disequilibrium block (D’> 0.9) generated by Haploview v4.0 (http://www.broad.mit.edu/mpg/haploview) using the control group data of the current study (n = 502). SNPs with red letter indicate a significant association with nominal p-values < 0.05.
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pone.0139413.g002: Relative positions of the ST8SIA2 single nucleotide polymorphisms (SNPs) analyzed in the current study and previous studies reporting positive associations with schizophrenia or bipolar disorder.BD-I, bipolar I disorder; BD, bipolar disorder. Relative positions of the exons are displayed in the left column. Colored area is the covered area of the gene in the corresponding study. Box with bold outline indicates high linkage disequilibrium block (D’> 0.9) generated by Haploview v4.0 (http://www.broad.mit.edu/mpg/haploview) using the control group data of the current study (n = 502). SNPs with red letter indicate a significant association with nominal p-values < 0.05.

Mentions: In the present study, we found suggestive associations between ST8SIA2 and schizophrenia and BD-I in the Korean population. Through fine mapping of the gene with tag SNPs and additional candidate SNPs, we identified 14 associated variants with at least a nominal level of significance in a diagnostic group, however none of them survived after multiple testing correction; these association trends were strongest in the combined schizophrenia and BD-I group. The strongest association was observed between rs11637898 and schizophrenia and BD-I under the dominant model, and the association with combined schizophrenia and the BD-I group remained significant after correcting for multiple testing. These results are consistent with a previous study of the Australian population revealing an association trend between several SNPs in ST8SIA2 and BD [15]. Two of these SNPs (rs11637898 and rs2168351) overlapped with SNPs showing association signals in the present study. Consistency between the two studies was also observed for two more pairs of SNPs with high linkage disequilibrium, i.e., rs4777980–rs11074070 and rs8037133–rs3784735. Fig 2 presents the relative positions of the ST8SIA2 SNPs that have been studied in schizophrenia and/or BD.


Association between ST8SIA2 and the Risk of Schizophrenia and Bipolar I Disorder across Diagnostic Boundaries.

Yang SY, Huh IS, Baek JH, Cho EY, Choi MJ, Ryu S, Kim JS, Park T, Ha K, Hong KS - PLoS ONE (2015)

Relative positions of the ST8SIA2 single nucleotide polymorphisms (SNPs) analyzed in the current study and previous studies reporting positive associations with schizophrenia or bipolar disorder.BD-I, bipolar I disorder; BD, bipolar disorder. Relative positions of the exons are displayed in the left column. Colored area is the covered area of the gene in the corresponding study. Box with bold outline indicates high linkage disequilibrium block (D’> 0.9) generated by Haploview v4.0 (http://www.broad.mit.edu/mpg/haploview) using the control group data of the current study (n = 502). SNPs with red letter indicate a significant association with nominal p-values < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4587961&req=5

pone.0139413.g002: Relative positions of the ST8SIA2 single nucleotide polymorphisms (SNPs) analyzed in the current study and previous studies reporting positive associations with schizophrenia or bipolar disorder.BD-I, bipolar I disorder; BD, bipolar disorder. Relative positions of the exons are displayed in the left column. Colored area is the covered area of the gene in the corresponding study. Box with bold outline indicates high linkage disequilibrium block (D’> 0.9) generated by Haploview v4.0 (http://www.broad.mit.edu/mpg/haploview) using the control group data of the current study (n = 502). SNPs with red letter indicate a significant association with nominal p-values < 0.05.
Mentions: In the present study, we found suggestive associations between ST8SIA2 and schizophrenia and BD-I in the Korean population. Through fine mapping of the gene with tag SNPs and additional candidate SNPs, we identified 14 associated variants with at least a nominal level of significance in a diagnostic group, however none of them survived after multiple testing correction; these association trends were strongest in the combined schizophrenia and BD-I group. The strongest association was observed between rs11637898 and schizophrenia and BD-I under the dominant model, and the association with combined schizophrenia and the BD-I group remained significant after correcting for multiple testing. These results are consistent with a previous study of the Australian population revealing an association trend between several SNPs in ST8SIA2 and BD [15]. Two of these SNPs (rs11637898 and rs2168351) overlapped with SNPs showing association signals in the present study. Consistency between the two studies was also observed for two more pairs of SNPs with high linkage disequilibrium, i.e., rs4777980–rs11074070 and rs8037133–rs3784735. Fig 2 presents the relative positions of the ST8SIA2 SNPs that have been studied in schizophrenia and/or BD.

Bottom Line: Thirty-one tag single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing significant associations in previous studies were genotyped.Fourteen of 34 SNPs showed a nominally significant association (p < 0.05) with at least one diagnostic group.Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.

ABSTRACT

Background: Findings from family studies and recent genome-wide association studies have indicated overlap in the risk genes between schizophrenia and bipolar disorder (BD). After finding a linkage between the ST8SIA2 (ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sicalyltransferase 2 gene) locus (15q26) and mixed families with schizophrenia and BD, several studies have reported a significant association between this gene and schizophrenia or BD. We investigated the genetic association between ST8SIA2 and both schizophrenia and BD in the Korean population.

Methods: A total of 582 patients with schizophrenia, 339 patients with BD, and 502 healthy controls were included. Thirty-one tag single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing significant associations in previous studies were genotyped. The associations were evaluated by logistic regression analysis using additive, dominant, and recessive genetic models.

Results: Fourteen of 34 SNPs showed a nominally significant association (p < 0.05) with at least one diagnostic group. These association trends were strongest for the schizophrenia and combined schizophrenia and bipolar I disorder (BD-I) groups. The strongest association was observed in rs11637898 for schizophrenia (p = 0.0033) and BD-I (p = 0.0050) under the dominant model. The association between rs11637898 and the combined schizophrenia and BD-I group (p = 0.0006, under the dominant model) remained significant after correcting for multiple testing.

Discussion: We identified a possible role of ST8SIA2 in the common susceptibility of schizophrenia and BD-I. However, no association trend was observed for bipolar II disorder. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

No MeSH data available.


Related in: MedlinePlus