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	Willour, V. L.,2009 PMID: 18180755
Citation	Willour, V. L., H. Chen, et al. (2009). Family-based association of FKBP5 in bipolar disorder. Mol Psychiatry 14(3): 261-268.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	1188 subjects from 317 nuclear families
SNP/Region/Marker Size	9 SNPs
Predominant Ethnicity
Population	Chicago, Hopkins,CHIP,CNG,NIMH collections

Detail Info

Sample Diagnosis	RDC and DSM
Sample Status	We selected 1188 subjects from 317 nuclear families for genotyping. They constituted all available independent trios (two parents and one affected child) and quads (two parents and two affected children) from among the subjects originally ascertained as part of the Chicago, Hopkins, NIMH Intramural Program (CHIP) bipolar disorder study,the Clinical Neurogenetics (CNG) Bipolar Disorder Study,or the National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative Study.All were ascertained on the basis of multiple relatives affected with a major mood disorder; the detailed description of the ascertainment and assessment protocols for each of these studies can be found in the initial study reports. All subjects signed IRBapproved written informed consent forms prior to enrolling in the studies. For the purposes of this study, we considered those with bipolar I disorder (BPI), bipolar II disorder (BPII) with recurrent major depression or schizoaffective disorder, manic or bipolar type (SA/BP) to be affected.The 1188 subjects contained 317 pedigrees and 491 offspring with BPI, 39 offspring with BPII and 24 offspring with SA/BP, resulting in 80 independent trios and 237 independent quads.
Technique	genotyping
Statistical Method	We examined the genotype data for deviations from Hardy-Weinberg equilibrium (HWE) using Haploview We tested for disease association with single SNPs using the FBAT.In addition, we performed genotypic transmission disequilibrium tests (TDT) using the gtrr function in STATA made available by David Clayton (http://www.gene.cimr.cam.ac.uk/clayton/software/stata). We also used exhaustive allelic TDT (EATDT) to test for evidence of haplotypic association.
Result Summary	Under an additive genetic model, rs4713902 showed significant overtransmission of the major allele (P=0.0001), which was consistent across the two sample sets (P=0.004 and 0.006). rs7757037 showed evidence of association that was strongest under the dominant model (P=0.001). This result was consistent across the two datasets (P=0.017 and 0.019). The dominant model yielded modest evidence for association (P<0.05) for three additional markers. Covariate-based analyses suggested that genetic variation within FKBP5 may influence attempted suicide and number of depressive episodes in bipolar subjects. Our results are consistent with the well-established relationship between the hypothalamic-pituitary-adrenal (HPA) axis, which mediates the stress response through regulation of cortisol, and mood disorders. Ongoing whole-genome association studies in bipolar disorder and major depression should further clarify the role of FKBP5 and other HPA genes in these illnesses.

SNPs reported by this study for BD (count: 9)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs3800373	FKBP5	A/C		FBAT: Additive model: major allele P-value = 0.060, minor allele P-value = 0.060; Dominant model: major allele P-value = 0.010, minor allele P-value = 0.452; Genotypic association: TDT P-value = 0.03	It showed a significant overtransmission under the dominant ...... It showed a significant overtransmission under the dominant model and a significant association in TDT result. More...	Positive
rs4713902	FKBP5	T/C		FBAT: Additive model: major allele P-value = 0.0001, minor allele P-value = 0.0001; Dominant model: major allele P-value = 0.019, minor allele P-value = 0.0007; Genotypic association: TDT P-value = 0.001	It showed a significant overtransmission of the major allele...... It showed a significant overtransmission of the major allele under both the additive model and the dominant model and a significant association in TDT result. More...	Positive
rs1360780	FKBP5	C/T		FBAT: Additive model: major allele P-value = 0.141, minor allele P-value = 0.141; Dominant model: major allele P-value = 0.057, minor allele P-value = 0.526; Genotypic association: TDT P-value = 0.13	No significant association was observed No significant association was observed	Negative
rs3798346	FKBP5	A/G		FBAT: Additive model: major allele P-value = 0.137, minor allele P-value = 0.137; Dominant model: major allele P-value = 0.177, minor allele P-value = 0.285; Genotypic association: TDT P-value = 0.35	No significant association was observed No significant association was observed	Negative
rs1043805	FKBP5	A/T		FBAT: Additive model: major allele P-value = 0.564, minor allele P-value = 0.564; Dominant model: major allele P-value = 0.365, minor allele P-value = 0.791; Genotypic association: TDT P-value = 0.53	No significant association was observed No significant association was observed	Negative
rs7757037	FKBP5	G/A		FBAT: Additive model: major allele P-value = 0.005, minor allele P-value = 0.005; Dominant model: major allele P-value = 0.310, minor allele P-value = 0.001; Genotypic association: TDT P-value = 0.007	It showed a significant overtransmission under the dominant ...... It showed a significant overtransmission under the dominant model and a significant association in TDT result. More...	Positive
rs6912833	FKBP5	T/A		FBAT: Additive model: major allele P-value = 0.335, minor allele P-value = 0.335; Dominant model: major allele P-value = 0.228, minor allele P-value = 0.654; Genotypic association: TDT P-value = 0.36	No significant association was observed No significant association was observed	Negative
rs9380525	FKBP5 MIR5690	C/G		FBAT: Additive model: major allele P-value = 0.110, minor allele P-value = 0.110; Dominant model: major allele P-value = 0.044, minor allele P-value = 0.496; Genotypic association: TDT P-value = 0.09	It showed a significant overtransmission under the dominant ...... It showed a significant overtransmission under the dominant model. More...	Positive
rs9296158	FKBP5	G/A		FBAT: Additive model: major allele P-value = 0.083, minor allele P-value = 0.083; Dominant model: major allele P-value = 0.020, minor allele P-value = 0.487; Genotypic association: TDT P-value = 0.05	It showed a significant overtransmission under the dominant ...... It showed a significant overtransmission under the dominant model. More...	Positive

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