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	Liu, X.,2010 PMID: 20215924
Citation	Liu, X., N. Akula, et al. (2010). "A genome-wide association study of amygdala activation in youths with and without bipolar disorder." J Am Acad Child Adolesc Psychiatry 49(1): 33-41.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	Thirty-nine patients with BD and 29 healthy controls
SNP/Region/Marker Size	104,043 SNPs
Predominant Ethnicity
Population	American
Gender	Number of males (proportion): 11 (0.38) for controls and 15 (0.39) for BD patients
Age Group	Adolescents : Age (mean,SD)(year): 9-18 (13 ,2.9) for controls and 9-19 (15,2.8) for BD patients

Detail Info

Sample Diagnosis	DSM
Sample Status	As detailed elsewhere,5 outpatients aged 9 to 19 years who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria15 for BD (n = 39) were studied along with 29 psychiatrically healthy volunteers . Compared to the study by Rich and colleagues,5 the sample in the present study included 25 additional subjects who were collected under the same inclusion criteria and scanned using the same paradigm. More than half of patients (n = 21, 53.9%) were euthymic (CDRS <40 and YMRS <12) at the time of testing; 33.3% (n = 13) were hypomanic (CDRS <40 and YMRS >12 but <26); 7.7% (n = 3) were depressed (CDRS >40 and YMRS <12); and 5.1% (n = 2) were in a mixed (CDRS >40 and YMRS >12) mood state. Most (n = 29, 74.4%) patients were medicated when scanned. Medications received were anticonvulsants (n = 22, 56.4%), atypical antipsychotics (n = 17, 43.6%), antidepressants (n = 13, 33.3%), lithium (n = 12, 30.8%), and stimulants (n = 8, 20.5%). Patients who had unstable medical illness, substance abuse within the previous 2 months, or pervasive developmental disorder were excluded. Healthy volunteers were excluded if they or their first-degree relatives had a positive psychiatric history. Subjects were self-identified as white (n = 57), African-American (n = 6), or unknown (n = 5).
Technique	Genotyping(Illumina) and fMRI
Statistical Method	Association analysis was carried out using PLINK software.After interesting markers were identified, cases were separated from controls in post hoc analyses to provide separate estimates of the regression coefficients for marker genotype versus amygdala activation in the case and control groups.Post hoc analyses examined associations between mood state and medications versus amygdala activity within the BD group. Specifically, Pearson correlations were used to examine the relation between amygdala activation and hypomania and depression scores and the number of medications taken by each patient.
Result Summary	Right amygdala activation under the hostility contrast was most strongly associated with an SNP in the gene DOK5 (rs2023454, p = 4.88 x 10(-7), false discovery rate = 0.05). DOK5 encodes a substrate of tropomyosin-related kinase B/C receptors involved in neurotrophin signaling. This SNP accounted for about 33% of the variance in youths with BD and 12% of the variance in healthy youths. Other results (false discovery rate <50%) were also observed at SNPs near several other genes. To our knowledge, this is the first genome-wide association study of amygdala activation in adolescents with BD. Although preliminary, these data suggest that DOK5 and perhaps several other genes influence the magnitude of amygdala activation during face processing, particularly in those with BD. Further studies are needed to replicate these findings and characterize the mechanisms involved.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs2023454	DOK5	C/G	C	Association analyses: in the right amygdala (P-value = 4.88E-07, FDR = 0.05)	This SNP was associated with amygdala activation under the h...... This SNP was associated with amygdala activation under the hostility contrast in the right amygdala. More...	Positive

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