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	Sjoholm, L. K.,2010 PMID: 20856823
Citation	Sjoholm, L. K., L. Backlund, et al. (2010). "CRY2 is associated with rapid cycling in bipolar disorder patients." PLoS One 5(9): e12632.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	patients with bipolar disorder type 1 (n = 497), patients with bipolar disorder type 2 (n = 60) ,patients with bipolar disorder with the feature rapid cycling (n = 155) and healthy blood donors (n = 1044)
SNP/Region/Marker Size	4 SNPs
Predominant Ethnicity	Caucasian
Population	Swedish
Gender	patients with bipolar disorder type 1 (43% men) ,patients with bipolar disorder type 2(36% men) and controls(59% men)

Detail Info

Sample Diagnosis	DSM
Sample Status	Patients (n= 577) were recruited from clinics in Stockholm County (n= 529), Southern Sweden (SkaÂ¡ne n =41), and Northern Sweden (Vasternorrland n= 7). They were diagnosed with bipolar disorder type 1 (n= 497, 43% men) or bipolar disorder type 2 (n= 60, 36% men), or bipolar disorder unknown type (n =20). All medical records were studied, and focusing on the most severe manic episode the DSM-IV manic symptoms as well as rapid cycling and mixed episodes were registered. Individuals were excluded if mania was the result of alcohol or drug abuse, medication or somatic disease, as well as if close relatives were already included. The phenotypes rapid cycling (n= 155, 35% men), mixed episodes, the age of onset of mania as well as depression were registered. Population control DNA samples were collected from anonymous blood donors (ABD, n= 1044, 59% men) at Karolinska University Hospital, Stockholm, Sweden. A previous study of samples collected in 2003 showed that the Swedish population had no strong internal genetic borders.
Technique	PCR and sequencing
Statistical Method	The three case-control sets and one follow-up case-case sample set were analyzed for allele frequency differences for the four CRY2 SNPs using logistic regression with gender as covariate.The trend tests with gender as covariate were performed in the Rcmdr package.
Result Summary	Family-based association test (FBAT) results for the dinucleotide repeat (GT)(N) polymorphism at position -1040 bp showed that allele A3 was preferentially transmitted to the affected individuals (Z=2.035 and P=.042). FBAT results for the val66met SNP showed a significant association for allele G (Z=3.415 and P=.00064). Transmission/disequilibrium test (TDT) haplotype analysis showed a significant result for the 3-G allele combination (P=.000394), suggesting that a DNA variant in the vicinity of the BDNF locus confers susceptibility to BP. Given that there is no direct evidence that either of the polymorphisms we examined alters function, it is unlikely that the actual risk-conferring allele is from these two sites. Rather, the causative site is likely nearby and in linkage disequilibrium with the 3-G haplotype that we have identified.

SNPs reported by this study for BD (count: 4)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs10838524	CRY2	A/G		Association analysis: allele P-value = 0.0076, empirical P-value = 0.022, OR [95% CI]=1.42[1.1021.83]; genotype, Cochran-Armitage trend P-value = 0.0076, Logistic regression: Dominant model, P-value = 0.0081, OR[95%CI]=1.79[1.1622.75], Recessive model, P-value = 0.1, OR[95%CI]=1.42[0.9322.16]	Significant association was found in BD. Significant association was found in BD.	Positive
rs10838527	CRY2 MAPK8IP1	G/A		Association analysis: allele P-value = 0.06, empirical P-value = 0.07, OR [95% CI]=1.51[0.9822.33]; genotype, Cochran-Armitage trend P-value = 0.039, Logistic regression: Dominant model, P-value = 0.046, OR[95%CI]=1.56[1.0122.42]	Significant association was found in BD. Significant association was found in BD.	Positive
rs3824872	CRY2 MAPK8IP1	A/C		Association analysis: allele P-value = 0.32, empirical P-value = 0.37, OR [95% CI]=1.51[0.8621.56]; genotype, Cochran-Armitage trend P-value = 0.32, Logistic regression: Dominant model, P-value = 0.86, OR[95%CI]=1.03[0.7121.49], Recessive model, P-value = 0.025, OR[95%CI]=2.16[1.1024.22]	Significant association was found in BD. Significant association was found in BD.	Positive
rs7123390	CRY2	A/G		Association analysis: allele P-value = 0.16, empirical P-value = 0.26, OR [95% CI]=1.29[0.9321.58]; genotype, Cochran-Armitage trend P-value = 0.16, Logistic regression: Dominant model, P-value = 0.23, OR[95%CI]=1.24[0.8721.78], Recessive model, P-value = 0.26, OR[95%CI]=1.39[0.7822.49]	No significant association was observed in BD. No significant association was observed in BD.	Negative

Haplotypes reported by this study for BD (count: 5)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs10838524 - rs7123390 - rs10838527 - rs3824872	G-A-A-C	CRY2	Haplotype association analysis:Logistic regression P-value = 0.49, OR=0.8	No significant association was found . No significant association was found .	Negative
rs10838524 - rs7123390 - rs10838527 - rs3824872	G-G-A-C	CRY2	Haplotype association analysis:Logistic regression P-value = 0.024, OR=0.75	Significant association was found in BD. Significant association was found in BD.	Positive
rs10838524 - rs7123390 - rs10838527 - rs3824872	A-A-A-C	CRY2	Haplotype association analysis:Logistic regression P-value = 0.043, OR=1.34	Significant association was found in BD. Significant association was found in BD.	Positive
rs10838524 - rs7123390 - rs10838527 - rs3824872	A-G-A-A	CRY2	Haplotype association analysis:Logistic regression P-value = 0.74, OR=0.94	No significant association was found . No significant association was found .	Negative
rs10838524 - rs7123390 - rs10838527 - rs3824872	A-G-G-A	CRY2	Haplotype association analysis:Logistic regression P-value = 0.048, OR=1.55	Significant association was found in BD. Significant association was found in BD.	Positive

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