Study Report

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Basic Info

Reference	Shink, E.,2005(a) PMID: 15768393
Citation	Shink, E., M. Harvey, et al. (2005). Analysis of microsatellite markers and single nucleotide polymorphisms in candidate genes for susceptibility to bipolar affective disorder in the chromosome 12Q24.31 region. Am J Med Genet B Neuropsychiatr Genet 135B(1): 50-58.
Disease Type	Bipolar Disorder
Study Design	case-control and family-based
Study Type	Candidate-region linkage study and candidate-gene association study
Sample Size	485 individuals from 41 families for linkage analysis;a case/control sample consisting of 213 patients and 177 controls for association analysis
SNP/Region/Marker Size	20 microsatellite markers and 22 SNPs
Predominant Ethnicity	Caucasian
Population	Canadian
Gender	In case/control sample:213 individuals from the SLSJ region (60% female in BPI patients,55% female in BPII patients)
Age Group	Adults : mean age at onset/year:28(SD=11) in BPI patients and 27(SD=11) in BPII patients

Detail Info

Sample Diagnosis	DSM
Sample Status	For linkage analysis we ascertained 485 individuals from 41 families of the SLSJ region of Quebec. This collection included 21 small pedigrees, totalizing 101 sampled persons never before used for linkage analysis. Diagnoses among the whole genotyped individuals were distributed as follows: 105 bipolar I (BPI) or schizoaffective disorder, bipolar type (Scz), 42 bipolar II (BPII), 54 recurrent unipolar major depression (RUP), and 57 cases of single episode major depression.For association analysis,a case/control sample consisting of 213 individuals(182 with BPI,32 with BPII) from the SLSJ region was established.Although most of the case subjects had a family history of affective disorders, they were all unrelated within immediate generations. Eleven spouses diagnosed as normal and without child with major affective disorder diagnosis were included in the control group. The remainder of controls subjects (n=177), all from the SLSJ region, were recruited from non-psychiatric genetic projects, since there is no significant gain of power to screen controls for psychiatric disorders with a lifetime risk of about 1% [Owen et al., 1997] and, as far as we could ascertain were representative of the general population. No attempt was made to match the controls and cases by age. Chi-squared test on 2*2 contingency table displayed no significant difference between distributions of gender in the case and control groups (P=0.318).
Technique	DHPLC and genotyping
Statistical Method	Two hierarchical affection status models (ASM) were used to define the affected phenotype for linkage analysis.The MFLINK software package (version 2.0) was used for linkage analysis with microsatellite markers.For association analysis,the usual chi-squared statistic on the raw contingency table (T1 statistic) and the largest chi-squared statistic calculated by comparing one column of the original table against the total of the other columns (T3 statistic) were utilized.As for microsatellite markers, the association hypothesis with SNPs was tested with CLUMP.
Result Summary	Two uncommon polymorphisms (minor allele frequency < or = 0.03) found in KIAA1595 and FLJ22471 genes, gave P-values below 0.05 with the T1 statistic. Moreover, using haplotype analysis, a nearly significant haplotypic association was observed at the HM74 gene. These results do not give strong support for a role in the susceptibility to bipolar disorder of any of these genes analyzed. However, the significance of rare polymorphisms should be explored by further analyses.

Other variants reported by this study for BD (count: 22)

Variant Name	Related Gene	Type	Allele Change	Statistical Values	Author Comments	Result Category
FLJ22471 GC32E04A	CCDC92	point mutation	A/G	Allelic analysis: T1 P-value = 1;genotypic analysis: T1 P-value = 0.001, T3 P-value = 0.287	Significant associations were found in genotypic analysis. Significant associations were found in genotypic analysis.	Positive
KIAA1595 GC29E06A	DDX55	point mutation	A/G	Allelic analysis: T1 P-value = 0.129;genotypic analysis: T1 P-value = 0.027, T3 P-value = 0.078	Significant associations were found in genotypic analysis. Significant associations were found in genotypic analysis.	Positive
FLJ11021 GC6E04A	RSRC2	point mutation	A/G	Allelic analysis: T1 P-value = 1;genotypic analysis: T1 P-value = 1, T3 P-value = 1	No significant association was observed. No significant association was observed.	Negative
FLJ22471 GC32E03A	CCDC92	point mutation	A/T	Allelic analysis: T1 P-value = 0.228;genotypic analysis: T1 P-value = 0.365, T3 P-value = 0.385	No significant association was observed. No significant association was observed.	Negative
HM74 GC10E01A	HCAR3	point mutation	A/C	Allelic analysis: T1 P-value = 0.644;genotypic analysis: T1 P-value = 0.66, T3 P-value = 0.659	No significant association was observed. No significant association was observed.	Negative
HM74 GC10E01B	HCAR3	point mutation	C/T	Allelic analysis: T1 P-value = 0.24;genotypic analysis: T1 P-value = 0.148, T3 P-value = 0.168	No significant association was observed. No significant association was observed.	Negative
KIAA1595 GC29E04A	DDX55	point mutation	C/G	Allelic analysis: T1 P-value = 0.572;genotypic analysis: T1 P-value = 0.587, T3 P-value = 0.587	No significant association was observed. No significant association was observed.	Negative
HM74a GC09E01B	HCAR2	point mutation	C/T	Allelic analysis: T1 P-value = 0.35;genotypic analysis: T1 P-value = 0.645, T3 P-value = 0.631	No significant association was observed. No significant association was observed.	Negative
KNTC1 GC07E08A	KNTC1	point mutation	G/T	Allelic analysis: T1 P-value = 1;genotypic analysis: T1 P-value = 0.251, T3 P-value = 0.462	No significant association was observed. No significant association was observed.	Negative
KIAA1595 GC29E08A	DDX55	point mutation	A/G	Allelic analysis: T1 P-value = 0.178;genotypic analysis: T1 P-value = 0.393, T3 P-value = 0.354	No significant association was observed. No significant association was observed.	Negative
HM74 GC10E01D	HCAR3	point mutation	A/G	Allelic analysis: T1 P-value = 0.714;genotypic analysis: T1 P-value = 0.785, T3 P-value = 0.781	No significant association was observed. No significant association was observed.	Negative
HM74 GC10E01C	HCAR3	point mutation	A/G	Allelic analysis: T1 P-value = 0.079;genotypic analysis: T1 P-value = 0.213, T3 P-value = 0.215	No significant association was observed. No significant association was observed.	Negative
HM74a GC09E01A	HCAR2	point mutation	A/G	Allelic analysis: T1 P-value = 0.289;genotypic analysis: T1 P-value = 0.382, T3 P-value = 0.207	No significant association was observed. No significant association was observed.	Negative
HM74 GC10E01E	HCAR3	point mutation	C/G	Allelic analysis: T1 P-value = 0.52;genotypic analysis: T1 P-value = 0.533, T3 P-value = 0.383	No significant association was observed. No significant association was observed.	Negative
RSN GC04E19A	CLIP1	point mutation	A/C	Allelic analysis: T1 P-value = 0.325;genotypic analysis: T1 P-value = 0.319, T3 P-value = 0.319	No significant association was observed. No significant association was observed.	Negative
RSN GC04E14A	CLIP1	point mutation	C/G	Allelic analysis: T1 P-value = 0.776;genotypic analysis: T1 P-value = 0.071, T3 P-value = 0.073	No significant association was observed. No significant association was observed.	Negative
ATP6V0A2 TJ6 GC24E19A	ATP6V0A2	point mutation	A/G	Allelic analysis: T1 P-value = 0.76;genotypic analysis: T1 P-value = 0.754, T3 P-value = 0.754	No significant association was observed. No significant association was observed.	Negative
SBNO1 GC22E16A	SBNO1	point mutation	A/G	Allelic analysis: T1 P-value = 0.779;genotypic analysis: T1 P-value = 0.908, T3 P-value = 0.888	No significant association was observed. No significant association was observed.	Negative
KNTC1 GC07E57A	KNTC1	point mutation	G/T	Allelic analysis: T1 P-value = 1;genotypic analysis: T1 P-value = 0.097, T3 P-value = 0.363	No significant association was observed. No significant association was observed.	Negative
KNTC1 GC07E25A	KNTC1	point mutation	C/G	Allelic analysis: T1 P-value = 0.806;genotypic analysis: T1 P-value = 0.835, T3 P-value = 0.835	No significant association was observed. No significant association was observed.	Negative
RSN GC04E12A	CLIP1	point mutation	A/G	Allelic analysis: T1 P-value = 0.845;genotypic analysis: T1 P-value = 0.652, T3 P-value = 0.621	No significant association was observed. No significant association was observed.	Negative
PITPNM2 GC18E01A	PITPNM2	point mutation	A/G	Allelic analysis: T1 P-value = 0.23;genotypic analysis: T1 P-value = 0.235, T3 P-value = 0.235	No significant association was observed. No significant association was observed.	Negative

Genes reported by this study for BD (count: 10)

Gene	Statistical Values/Author Comments	Result Category
CLIP1	We found no polymorphisms associated with bipolar disorder in this gene. We found no polymorphisms associated with bipolar disorder in this gene.	Negative
ATP6V0A2	We found no polymorphisms associated with bipolar disorder in this gene. We found no polymorphisms associated with bipolar disorder in this gene.	Negative
DDX55	We found polymorphisms associated with bipolar disorder in this gene. We found polymorphisms associated with bipolar disorder in this gene.	Positive
KNTC1	We found no polymorphisms associated with bipolar disorder in this gene. We found no polymorphisms associated with bipolar disorder in this gene.	Negative
RSRC2	We found no polymorphisms associated with bipolar disorder in this gene. We found no polymorphisms associated with bipolar disorder in this gene.	Negative
CCDC92	We found polymorphisms associated with bipolar disorder in this gene. We found polymorphisms associated with bipolar disorder in this gene.	Positive
PITPNM2	We found no polymorphisms associated with bipolar disorder in this gene. We found no polymorphisms associated with bipolar disorder in this gene.	Negative
HCAR2	We found no polymorphisms associated with bipolar disorder in this gene. We found no polymorphisms associated with bipolar disorder in this gene.	Negative
HCAR3	We found no polymorphisms associated with bipolar disorder in this gene. We found no polymorphisms associated with bipolar disorder in this gene.	Negative
SBNO1	We found no polymorphisms associated with bipolar disorder in this gene. We found no polymorphisms associated with bipolar disorder in this gene.	Negative

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