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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Basic Info

Reference	Schulze, T. G.,2009 PMID: 19088739
Citation	Schulze, T. G., S. D. Detera-Wadleigh, et al. (2009). Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder. Mol Psychiatry 14(5): 487-491.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	number of case/control:745/830 in German sample,457/562 in NIMH 1-4 sample,466/212 in NIMH 5 sample
SNP/Region/Marker Size	2 SNPs
Predominant Ethnicity	Caucasian
Population	German and NIMH collection
Gender	male/female:401/344 in cases and 447/383 in controls for German sample,166/291 in cases and 315/247 in controls for NIMH 1-4 sample,237/229 in cases and 119/93 in controls for NIMH 5 sample
Age Group	Adults : mean age(year):44(SD=13)in cases and 49(SD=16) in controls for German sample,41(SD=11)in cases and 57(SD=17) in controls for NIMH 1-4 sample,43(SD=13)in cases and 51(SD=17) in controls for NIMH 5 sample

Detail Info

Sample Diagnosis	DSM
Sample Status	German case-case control sample:This sample was used in our previous GWAS analysis. Detailed ascertainment and phenotype information was presented in Baum et al.2 For the present study, 745 cases (401 men, 344 women; mean age 44[SD=13]) with Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)-defined bipolar 1 disorder from consecutive hospital admissions and 830 population-based control individuals (447 men, 383 women; mean age 49[SD=16]) were available. NIMH 1-4 case-control sample. This sample was used in our previous GWAS analysis.Cases were drawn from waves 1 through 4 of the National Institute of Mental Health (NIMH) Genetics Initiative (http://nimhgenetics.org), a sample of multiplex families ascertained through sibling pairs with bipolar 1 or schizoaffective BD. One proband per family was selected for study, as detailed in Baum et al.2 The control sample was also ascertained by the NIMH Genetics Initiative with the help of a marketing firm. NIMH 5 case-control sample. This constitutes an additional sample that has previously not been used in our studies. Both cases and controls were recruited within the framework of wave 5 of the NIMH Genetics Initiative. The ascertainment scheme allowed for the inclusion of unrelated subjects with a diagnosis of DSM-IV bipolar I disorder or SABP, without regard to family history. Controls consisted of volunteers collected by the NIMH Genetics Initiative who were not available at the time of our initial study. All subjects were of European descent and were collected under protocols approved by the local Institutional Review Boards.
Technique	genotyping
Statistical Method	PLINK (version 1.03) was used for primary association testing and to assess deviation from Hardy-Weinberg equilibrium. Analyses were performed for each sample individually. Linkage disequilibrium(LD) between the two SNPs was calculated using the UNPHASED 3.08 software.A Mantel-Haenszel random effects meta-analysis,implemented in Review Manager,was used to assess association between BD and the two ANK3 SNPs in multiple samples. Heterogeneity between the samples was assessed using the I² statistic.
Result Summary	Our previously reported findings at rs9804190, which had been based on DNA pooling, were confirmed by individual genotyping in the National Institute of Mental Health (NIMH) waves 1-4 (P=0.05; odds ratio (OR)=1.24) and German (P=0.0006; OR=1.34) samples. This association was replicated in an independent US sample known as NIMH wave 5 (466 cases, 212 controls; P=0.017; OR=1.38). A random-effects meta-analysis of all three samples was significant (P=3 x 10(-6); OR=1.32), with no heterogeneity. Individual genotyping of rs10994336 revealed a significant association in the German sample (P=0.0001; OR=1.70), and similar ORs in the NIMH 1-4 and NIMH 5 samples that were not significant at the P<0.05 level. Meta-analysis of all three samples supported an association with rs10994336 (P=1.7x 10(-5); OR=1.54), again with no heterogeneity. There was little linkage disequilibrium between the two markers. Further analysis suggested that each marker contributed independently to BD, with no significant marker x marker interaction. Our findings strongly support ANK3 as a BD susceptibility gene and suggest true allelic heterogeneity.

SNPs reported by this study for BD (count: 2)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs10994336	ANK3	C/T		single marker case-control association: in German sample, P-value(OR)=0.112 (1.39), in NIMH 1-4 sample, P-value(OR)=0.241 (1.33), in NIMH 5 sample, P-value(OR)=0.241 (1.33)	Significant association was observed Significant association was observed	Positive
rs9804190	ANK3	C/T		single marker case-control association: in German sample, P-value(OR)=0.050 (1.24), in NIMH 1-4 sample, P-value(OR)=0.017 (1.38), in NIMH 5 sample, P-value(OR)=0.017 (1.38)	Significant association was observed Significant association was observed	Positive

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