BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Study Report

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Basic Info

Reference	Dedman, A.,2012 PMID: 22328486
Citation	Dedman, A., A. McQuillin, et al. (2012). "Sequencing of the ANKYRIN 3 gene (ANK3) encoding ankyrin G in bipolar disorder reveals a non-conservative amino acid change in a short isoform of ankyrin G." Am J Med Genet B Neuropsychiatr Genet 159B(3): 328-335.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	The UCL1 sample comprised of 506 subjects with bipolar 1 (BP1) disorder and 510 matched control subjects.
SNP/Region/Marker Size	135 SNPs
Predominant Ethnicity	Caucasian
Population	English, Irish, Welsh, and Scottish
Gender	38% males in cases for UCL1 sample and 37% males for UCL2 sample
Age Group	Adults : Mean Age of Onset(year):22.53 for UCL1 cases and 22.80 for UCL2 cases

Detail Info

Sample Diagnosis	RDC
Sample Status	Subject recruitment for the UCL1 sample has been described in detail previously [Sklar et al., 2008]. Briefly, the UCL1 sample comprised of 506 subjects with bipolar 1 (BP1) disorder and 510 matched control subjects. Both cases and controls were ancestrally selected to be of English, Irish, Welsh, or Scottish ancestry. U.K. The replication cohort (UCL2) comprised 593 bipolar research subjects diagnosed with bipolar I or bipolar II disorder and 162 screened control subjects screened for an absence of psychiatric disorders plus 480 unscreened British control subjects from the European Collection of Cell Cultures (ECACC).
Replication Size	The UCL2 sample comprised 593 bipolar patients and 642 control subjects
Technique	Genotyping
Statistical Method	Genotypic and allelic associations for SNPs were tested using c2 tests. Fisher's exact tests were performed using the "fisher.test" function in R [R Development Core Team, 2011]. Haplotype tests of association were performed using Haploview [Barrett et al., 2005]. Meta-analysis was performed using PLINK [Purcell et al., 2007].
Result Summary	None of the SNPs previously associated with bipolar disorder were associated in the UCL2 sample. One of the four SNPs associated in the UCL1 sample, rs1938526, was still significantly associated with bipolar disorder when the UCL1 and UCL2 samples were combined (P = 0.0095). The results demonstrate the impact of heterogeneity on replication of allelic associations even within well-defined ancestral populations. DNA sequencing revealed a novel low frequency (0.007) ANK3 SNP (ss469104599) which causes a non-conservative amino acid change at position 794 in the shorter isoforms of the ankyrin G protein. Protein-function analysis software predicted the amino acid change to be "probably damaging" and it could therefore be detrimental to the function of this isoform. Given that there was only a modest increase in the allele frequency of ss469104599 in cases compared to controls further association studies are needed in additional samples to establish a possible etiological role for this amino acid change.

SNPs reported by this study for BD (count: 14)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs61845768	ANK3			Association analysis: for UCL1 sample, chi square=0.0103, P-value = 0.92, OR=0.94; for UCL2 sample, chi square=0.116, P-value = 0.73, OR=0.79; for UCL1+UCL2 sample, chi square=0.0666, P-value = 0.8, OR=0.89	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs10994397	ANK3	T/C		Association analysis: for UCL1 sample, P-value = 0.001, OR=1.61; for UCL2 sample, P-value = 0.53, OR=1.13; for UCL1+UCL2 sample, P-value = 0.017, OR=1.32	Significant association was observed in BD. Significant association was observed in BD.	Positive
rs10994336	ANK3	T/C		Association analysis: for UCL1 sample, P-value = 0.013, OR=1.63; for UCL2 sample, P-value = 0.93, OR=1.02; for UCL1+UCL2 sample, P-value = 0.048, OR=1.28	Significant association was observed in BD. Significant association was observed in BD.	Positive
rs10994285	ANK3	T/C		Association analysis: for UCL1 sample, P-value = 0.041, OR=1.58; for UCL2 sample, P-value = 0.91, OR=0.976; for UCL1+UCL2 sample, P-value = 0.11, OR=1.28	Significant association was observed in BD. Significant association was observed in BD.	Positive
rs10821792	ANK3	A/G		Association analysis: for UCL1 sample, P-value = 0.033, OR=1.48; for UCL2 sample, P-value = 0.44, OR=1.13; for UCL1+UCL2 sample, P-value = 0.02, OR=1.31	Significant association was observed in BD. Significant association was observed in BD.	Positive
rs10821668	ANK3			Association analysis: for UCL1 sample, chi square=2.013, P-value = 0.16, OR=0.86; for UCL2 sample, chi square=0.134, P-value = 0.71, OR=1.04; for UCL1+UCL2 sample, chi square=0.69, P-value = 0.41, OR=0.94	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs41274672	ANK3			Association analysis: for UCL1 sample, chi square=0.638, P-value = 0.42, OR=1.47; for UCL2 sample, chi square=1.226, P-value = 0.27, OR=0.65; for UCL1+UCL2 sample, chi square=0.0392, P-value = 0.84, OR=0.94	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs28932171	ANK3			Association analysis: for UCL1 sample, chi square=0.542, P-value = 0.46, OR=1.11; for UCL2 sample, chi square=0.387, P-value = 0.53, OR=0.92; for UCL1+UCL2 sample, chi square=0.201, P-value = 0.65, OR=1.01	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2018783	ANK3	G/A		Association analysis: for UCL1 sample, P-value = 0.043, OR=1.2; for UCL2 sample, P-value = 0.92, OR=1.01; for UCL1+UCL2 sample, P-value = 0.089, OR=1.11	Significant association was observed in BD. Significant association was observed in BD.	Positive
rs1938526	ANK3	G/A		Association analysis: for UCL1 sample, P-value = 0.008, OR=1.65; for UCL2 sample, P-value = 0.39, OR=1.17; for UCL1+UCL2 sample, P-value = 0.0095, OR=1.4	Significant association was observed in BD. Significant association was observed in BD.	Positive
rs185539081	ANK3	G/C		Association analysis: for UCL1 sample, OR=0.93, P-Chi-square Pearson=0.96, P-Chi-square Fisher Exact Test=1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs142415903	ANK3	G/A		Association analysis: for UCL1 sample, OR=0.94, P-Chi-square Pearson=0.93, P-Chi-square Fisher Exact Test=1	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs139092048	ANK3	C/A		Association analysis: for UCL1 sample, OR=0.81, P-Chi-square Pearson=0.69, P-Chi-square Fisher Exact Test=0.8	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11599164	ANK3			Association analysis: for UCL1 sample, chi square=0.433, P-value = 0.51, OR=1.1; for UCL2 sample, chi square=0.492, P-value = 0.48, OR=0.9; for UCL1+UCL2 sample, chi square=0.00843, P-value = 0.93, OR=0.99	No significant association was observed in BD. No significant association was observed in BD.	Negative

Genes reported by this study for BD (count: 1)