Study Report

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Basic Info

Reference	Grover, D.,2009 PMID: 19160447
Citation	Grover, D., R. Verma, et al. (2009). Family-based association of YWHAH in psychotic bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 150B(7): 977-983.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	1211 subjects from 318 nuclear families [bipolar I disorder (BPI) (N=491), schizoaffective disorder bipolar type(SABP) (N=24), or bipolar II disorder (BPII) (N=39)].
SNP/Region/Marker Size	6 SNPs
Predominant Ethnicity
Population	American Collections

Detail Info

Sample Diagnosis	DSM
Sample Status	1,211 subjects from 318 nuclear families constituted all available independent trios and quads from subjects originally ascertained in three BP family studies: the Chicago, Hopkins, NIMH Intramural Program (CHIP) study[McInnis et al., 2003]; the Clinical Neurogenetics (CNG) study [Detera-Wadleigh et al., 1999]; and the NIMH Genetics Initiative BP Collaborative (NIMH) study [1997]. The 318 pedigrees yielded 554 affected offspring, consisting of 257 quads and 61 trios.
Technique	genotyping
Statistical Method	the Transmission Disequilibrium Test (TDT) and Likelihood ratio tests (LRTs)
Result Summary	Using a family-based association test, we found that rs2246704 was associated with BP (OR 1.31, P = 0.03) and psychotic BP (OR = 1.66, P = 0.002). The polymorphic repeat and two other SNPs were also modestly associated with psychotic BP. We have provided additional evidence for association of variants in YWHAH with major mental illness. Additional association analyses of larger sample sets will be required to clarify the role of YWHAH in schizophrenia and BP. The use of clinical sub-phenotypes such as psychotic features or other potential schizophrenia/BP overlap variables including cognitive abnormalities and poor functioning might shed further light on the potential subtypes of illness most closely associated with genetic variation in YWHAH.

Genetic factors reported by this study for BD

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

SNP	Related Gene(s)	Statistical Values	Author Comments	Result Category
rs2853884	YWHAH	Allelic Association Analysis P-value: 1.Standard BP: Major allele: 0.51(Additive Model), 0.86(Dominant Model); Minor allele: 0.51(Additive Model), 0.33(Dominant Model) 2.Psychotic BP: Major allele: 0.21(Additive Model), 0.73(Dominant Model); Minor allele: 0.21(Additive Model), 0.17(Dominant Model) 3.Mood-incongruent psychotic BP: Major allele: 0.44(Additive Model), 0.40(Dominant Model); Minor allele: 0.44(Additive Model), 0.68(Dominant Model)	No significant association was observed No significant association was observed	Negative
rs3747158	C22orf24 YWHAH	P-value: Genotypic transmission: 0.03 (psychotic BP) and Allelic transmission: 1.Standard BP: Major allele: 0.62(Additive Model), 0.80(Dominant Model); Minor allele: 0.62(Additive Model), 0.35(Dominant Model) 2.Psychotic BP: Major allele: 0.16(Additive Model), 0.93(Dominant Model); Minor allele: 0.16(Additive Model), 0.03(Dominant Model) 3.Mood-incongruent psychotic BP: Major allele: 0.84(Additive Model), 0.93(Dominant Model); Minor allele: 0.84(Additive Model), 0.718(Dominant Model)	It had evidence of association with BP that was impacted by ...... It had evidence of association with BP that was impacted by the psychotic features covariate. More...	Positive
rs2246704	YWHAH	P-value: Genotypic transmission: 0.03 (standard BP), 0.002 (psychotic BP)and Allelic transmission: 1.Standard BP: Major allele: 0.27(Additive Model), 0.57(Dominant Model); Minor allele: 0.27(Additive Model), 0.03(Dominant Model) 2.Psychotic BP: Major allele: 0.04(Additive Model), 0.82(Dominant Model); Minor allele: 0.04(Additive Model), 0.002(Dominant Model) 3.Mood-incongruent psychotic BP: Major allele: 0.92(Additive Model), 0.42(Dominant Model); Minor allele: 0.92(Additive Model), 0.57(Dominant Model)	Using a family-based association test, we found that rs22467...... Using a family-based association test, we found that rs2246704 was associated with BP (OR=1.31, P=0.03) and psychotic BP (OR=1.66, P=0.002). More...	Positive
rs4820059	C22orf24 YWHAH	P-value: Genotypic transmission: 0.008 (psychotic BP) and Allelic transmission: 1.Standard BP: Major allele: 0.47(Additive Model), 0.43(Dominant Model); Minor allele: 0.47(Additive Model), 0.10(Dominant Model) 2.Psychotic BP: Major allele: 0.07(Additive Model), 0.89(Dominant Model); Minor allele: 0.07(Additive Model), 0.008(Dominant Model) 3.Mood-incongruent psychotic BP: Major allele: 0.91(Additive Model), 0.67(Dominant Model); Minor allele: 0.91(Additive Model), 0.61(Dominant Model)	It had evidence of association with BP that was impacted by ...... It had evidence of association with BP that was impacted by the psychotic features covariate. More...	Positive
rs933226	C22orf24 YWHAH	Allelic Association Analysis P-value: 1.Standard BP: Major allele: 0.66(Additive Model), 0.79(Dominant Model); Minor allele: 0.66(Additive Model), 0.52(Dominant Model) 2.Psychotic BP: Major allele: 0.89(Additive Model), 0.50(Dominant Model); Minor allele: 0.89(Additive Model), 0.87(Dominant Model) 3.Mood-incongruent psychotic BP: Major allele: 0.54(Additive Model), 0.75(Dominant Model); Minor allele: 0.54(Additive Model), 0.39(Dominant Model)	No significant association was observed No significant association was observed	Negative

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
YWHAH 5'UTR (GCCTGCA)n	YWHAH	duplication	7-bp repeat		Allelic Association Analysis P-value:1.Standard BP: allele1:0.29(Additive Model), 0.14(Dominant Model);allele2:0.30(Additive Model), 1.00(Dominant Model) 2.Psychotic BP:allele1:0.04(Additive Model), 0.01(Dominant Model);allele2:0.05(Additive Model), 0.79(Dominant Model) 3.Mood-incongruent psychotic BP:allele1:0.83(Additive Model), 0.77(Dominant Model); allele2:0.92(Additive Model), 0.93(Dominant Model) LRT P-value:0.03(Psychotic features), 0.68(Mood-incongruent psychotic features)P-value 0.01 0.83 0.77	The polymorphic repeat was modestly associated with psychoti...... The polymorphic repeat was modestly associated with psychotic BP. More...	Positive

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

Gene	Statistical Values/Author Comments	Result Category
YWHAH	Our study adds to the evidence that YWHAH is implicated in both BP and schizophrenia. Our study adds to the evidence that YWHAH is implicated in both BP and schizophrenia.	Positive

Genetic factors reported by this study for SZ and/or MDD

SNPs reported by this study for SZ/MDD

Disease	SNP	Related Gene(s)	Statistical Values	Description	Result Category
SZ	rs933226	C22orf24 YWHAH	LRT P-value:0.44(Psychotic features), 0.82(Mood-incongruent psychotic features)	None of the SNPs showed any difference between observed and expected allelic transmissionswhen the mood-incongruent psychotic BP phenotype was used.And none of the SNPs were impacted by the moodincongruence covariate.	Negative
SZ	rs3747158	C22orf24 YWHAH	LRT P-value:0.01(Psychotic features), 0.82(Mood-incongruent psychotic features)	It had evidence of association with BP that was impacted by the psychotic features covariate.	Positive
SZ	rs4820059	C22orf24 YWHAH	LRT P-value:0.03(Psychotic features), 0.76(Mood-incongruent psychotic features)	It had evidence of association with BP that was impacted by the psychotic features covariate.	Positive
SZ	rs2246704	YWHAH	LRT P-value:0.02(Psychotic features), 0.30(Mood-incongruent psychotic features)	Using a family-based association test, we found that rs2246704 was associated with BP (OR=1.31, P=0.03) and psychotic BP (OR=1.66, P=0.002).None of the SNPs showed any difference between observed and expected allelic transmissionswhen the mood-incongruent psychotic BP phenotype was used.And none of the SNPs were impacted by the moodincongruence covariate.	Positive
SZ	rs2853884	YWHAH	LRT P-value:0.43(Psychotic features), 0.38(Mood-incongruent psychotic features)	None of the SNPs showed any difference between observed and expected allelic transmissionswhen the mood-incongruent psychotic BP phenotype was used.And none of the SNPs were impacted by the moodincongruence covariate.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	YWHAH	Our study adds to the evidence that YWHAH is implicated in both BP and schizophrenia.	Positive