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	Bureau A, 2013 PMID: 23602252
Citation	Bureau, A., Y. C. Chagnon, et al. (2013). "Follow-up of a Major Psychosis Linkage Site in 13q13-q14 Reveals Significant Association in Both Case-Control and Family Samples." Biol Psychiatry.
Disease Type	bipolar disorder & schizophrenia
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	The case-control sample consisted of 247 unrelated SZ patients and 250 unrelated normal control subjects from the Eastern Quebec population.
SNP/Region/Marker Size	2150 SNPs in 13q13-q14
Predominant Ethnicity	Caucasian
Population	French-Canadian
Gender	79% male cases, 78% male controls in the case-control sample

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	The case-control sample is from the Eastern Quebec population. All subjects were Caucasian of French-Canadian ancestry. The kindred sample consisted of 845 members from 48 multigenerational families, of which 21 were mainly affected by BD ( 15% of the affected family members had SZ), 15 were mainly affected by a SZ spectrum disorder ( 15% had BD), and 12 were mixed pedigrees, i.e., affected almost equally by SZ and BD. In the kindred sample, narrow and broad definitions of the SZ and BD phenotypes were used in the analyses. Age of onset in the kindred sample was defined as the age of the first definitive episode or the age of the first probable episode of a disorder from the spectrum of SZ and BD.
Replication Size	The kindred sample consisted of 845 members from 48 multigenerational families.
Technique	The case-control sample was genotyped using a customized Illumina genome-wide SNP array. Copy number variants were inferred from the genotyping probe signals using the hidden Markov model implemented in PennCNV. For replication in the kindred sample, SNPs were analyzed using an in-house minisequencing approach.
Statistical Method	Association analysis between phenotype and genotype was performed using standard allelic, trend, and genotypic tests under a dominant and an additive model. Allelic and genotypic odds ratios were estimated on the genotyped SNPs and on untyped SNPs imputed using genotype data from the 1000 Genomes Project. Allelic log-odds ratios (ORs) were estimated and Wald tests of association were performed under a logistic model estimated using generalized estimating equations (GEEs) with an independent working correlation structure between the subjects in the same family and an empirical variance estimate robust to intrafamilial correlation. The same approach was then applied to the combined case-control and family samples.
Result Summary	An association of the T allele of rs1156026 found in the case-control sample was replicated in the kindred sample, strengthening the overall association evidence. The effect size increased in the subset of unrelated patients with a family history and in the 15 families where SZ was predominant. In the kindred sample, onset of either SZ or BD was, on average, 5 years earlier for T/T compared with C/C homozygotes, leading to stronger association in patients with onset before 26 years of age. Case-control and family-based association provided evidence of a locus at 13q13-q14 related to SZ. The proximity of the associated single nucleotide polymorphism with the linkage signal and the extension of the associated phenotype to major psychosis with younger age of onset indicate congruence between the linkage and association signals. The rs1156026 association is novel and factors explaining its nondetection in previous studies are discussed.

SNPs reported by this study for BD (count: 2)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs1156026		T/C		P-value=0.012, OR (95% CI)=1.54 (1.1, 2.17) in all families of the kindred sample; P-value=8.5E-07, OR (95% CI)=1.69 (1.37, 2.08) for the combined analyses; P-value=6.4E-08, OR (95% CI)=1.85 (1.48, 2.31) for the combined analyses; P-value=0.76, OR (95% CI)=1.06 (0.75, 1.48)	An association of the T allele of rs1156026 found in the cas...... An association of the T allele of rs1156026 found in the case-control sample was replicated in the kindred sample, strengthening the overall association evidence. More...	Positive
rs2120753		G/A		P-value=0.18, OR (95% CI)=0.80 (0.58-1.11) in all families of the kindred sample; P-value=2.5E-04, OR (95% CI)=0.68 (0.56-0.84) for the combined analyses; P-value=1.1E-05, OR (95% CI)=0.63 (0.51-0 .77) for the combined analyses; P-value=0.61, OR (95% CI)=0.92 (0.65, 1.29)	No association of this SNP was replicated. No association of this SNP was replicated.	Negative