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	McAuley, E. Z.,2009 PMID: 19584773
Citation	McAuley, E. Z., J. M. Fullerton, et al. (2009). Association between the serotonin 2A receptor gene and bipolar affective disorder in an Australian cohort. Psychiatr Genet 19(5): 244-252.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	218 cases and 166 healthy controls
SNP/Region/Marker Size	12 SNPs
Predominant Ethnicity	Caucasian
Population	Australian

Detail Info

Sample Diagnosis	RDC
Sample Status	Our Australian case-control cohort consists of individuals who are almost entirely of British or Irish descent. Cases were recruited as part of an ongoing bipolar genetics study by the Mood Disorders Unit, Prince of Wales Hospital/School of Psychiatry, University of New South Wales. The majority of cases were from families that had been previously recruited for linkage analyses. Only one affected individual per family was selected for the case-control cohort. The remainder of the cases were selected from a specialized BP clinic, of whom 20% had a family history of BP. All patients were assessed using the Diagnostic Interview for Genetic Studies (Nurnberger et al., 1994). For controls, we selected the spouse or a completely unrelated pedigree member of each of the case individuals from the families. Each control individual was age matched to the corresponding case. The control individuals were also interviewed using the Diagnostic Interview for Genetic Studies.Blood was collected from 384 individuals and DNA was extracted using standard methods. Two hundred and eighteen had BP or related affective illnesses. The specific Research Diagnostic Criteria diagnoses were:158 individuals with bipolar I disorder (BPI), nine with schizoaffective disorder manic type (SZ/MA), 41 with bipolar II disorder (BPII), 10 with recurrent unipolar depression and 166 unaffected individuals. In total, 60% of cases had a positive family history for BP and 75% for some affective disorder.
Replication Size	1010 bipolar cases and 1034 controls
Technique	genotyping
Statistical Method	Statistical analyses were performed with the software PLINK v1.02:Hardy-Weinberg exact test statistics for each SNP.Association analysis was performed using two disease models.To devise empirical P values for association, 10 000 permutations were performed using the -mperm option. Haplotype analysis was performed with standard association testing using the-hap-assoc option, and with conditional regression-based haplotype association using the -chap option.
Result Summary	RESULTS: Significant association of rs2224721 (P = 0.02) and borderline significance of rs1923886 (P = 0.05) were observed. The former remained significant after multiple testing corrections using the rough False Discovery Rate method, but did not exceed the more conservative Bonferroni's correction threshold. Haplotype association analysis suggests that the haplotype CCGCA (at SNPs rs3125, rs6314, rs1923886, rs2224721 and rs2770296) is protective against bipolar disorder (P = 0.021, odds ratio 0.63) and the rarer haplotype CCACG confers risk to the disorder (P = 0.0065, odds ratio 3.08). CONCLUSION: We found that HTR2A is associated with bipolar disorder. The HTR2A gene should not be excluded as a potential susceptibility gene for bipolar disorder despite a number of conflicting association results.

SNPs reported by this study for BD (count: 8)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs2770296	HTR2A			single marker association: Asymptotic P-value = 0.26, Empirical P-value = 0.29, Odds ratio=1.2	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs2224721	HTR2A HTR2A-AS1			single marker association: Asymptotic P-value = 0.02, Empirical P-value = 0.02, Odds ratio=1.53	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs1928040	HTR2A			single marker association: Asymptotic P-value = 0.17, Empirical P-value = 0.17, Odds ratio=0.82	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs1923886	HTR2A HTR2A-AS1			single marker association: Asymptotic P-value = 0.05, Empirical P-value = 0.06, Odds ratio=0.75(P-value = 0.91 in replication sample from NIMH )	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs6314	HTR2A			single marker association: Asymptotic P-value = 0.31, Empirical P-value = 0.36, Odds ratio=0.78	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs985933	HTR2A			single marker association: Asymptotic P-value = 0.38, Empirical P-value = 0.4, Odds ratio=1.14	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs3125	HTR2A			single marker association: Asymptotic P-value = 0.85, Empirical P-value = 0.88, Odds ratio=1.04	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs6313	HTR2A			single marker association: Asymptotic P-value = 0.46, Empirical P-value = 0.49, Odds ratio=0.9	No significant allelic association with BP was found No significant allelic association with BP was found	Negative

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

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs3125 - rs6314 - rs1923886 - rs2224721 - rs2770296		HTR2A	haplotype analysis:global P-value = 0.03; (C-C-G-C-A):P-value = 0.02, OR=0.63; (C-C-A-C-G):P-value = 0.007, OR=3.08	We detected significant associations in BP group. We detected significant associations in BP group.	Positive

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