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	Zandi, P. P., 2007 PMID: 17357146
Citation	Zandi, P. P., D. Avramopoulos, et al. (2007). "SNP fine mapping of chromosome 8q24 in bipolar disorder." Am J Med Genet B Neuropsychiatr Genet 144B(5): 625-630.
Disease Type	Bipolar Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	155 nuclear families consisting of 352affected offsprings (273 with BPI, 56 with BPII, and 23 with SABP)
SNP/Region/Marker Size	288 SNPs
Predominant Ethnicity
Population	Johns Hopkins University collection and NIMH collection

Detail Info

Sample Diagnosis	Schedule for Affective Disorders (SADS), Diagnostic Interview for Genetic Studies (DIGS), DSM-III-R or DSM-IV criteria
Sample Status	The first sample was collected by the team of clinician investigators in the Mood Disorders Research Program at Johns Hopkins University. The families were ascertained by opportunistic means through a proband who had bipolar I disorder (BPI). The second sample of families was collected as part of the NIMH Genetics Initiative on Bipolar Disorder, a multi-site collaboration to ascertain and assess families using common procedures for genetic studies of BP. The initial sample includes 273 with BPI, 56 with BPII, and 23 with SABP and the replication sample consists of 192 with BPI, 30 with BPII, and 9 with SABP.
Replication Size	103 families with 231 affected offsprings (192 with BPI, 30 with BPII, and 9 with SABP)
Technique	genotyping using the Taqman platform with Assays-on-Demand or Assays-by-Design from Applied Biosystems
Statistical Method	They used FBAT to test each SNP separately for association with BP, HBAT to test haplotypes of SNPs for association with BP and the Genotype-IBD Sharing Test (GIST) to further analyze the SNP data and provide another test of association.
Result Summary	Two clusters of SNPs emerged with the strongest evidence of association. The first consisted of three SNPs, approximately 3 kb 5' from the gene ST3GAL1. These SNPs were associated with BP in the initial sample by FBAT (best P = 0.001) and GIST (best P = 0.05) and associated in the replication sample by FBAT (best P = 0.04). The second cluster consisted of four SNPs (one of which was not genotyped in the replication sample), approximately 480 kb 5' of ST3GAL1 in a relative gene desert. These SNPs were associated with BP in the initial sample by FBAT (best P = 0.007) and GIST (best P = 0.03), and marginally associated in the replication sample by FBAT (best P = 0.07) and GIST (P = 0.04). ST3GAL1 belongs to a family of glycosyltransferase proteins, several members of which are highly expressed in the brain and involved in neurogenesis. Several other interesting candidate genes are also located nearby. The congruence of findings across methods and samples suggests further investigation is warranted in these two targeted regions.

SNPs reported by this study for BD (count: 7)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs1457466	ST3GAL1	G/A		FBAT P-value = 0.078, GIST P-value > 0.05 in the initial sample; FBAT P-value = 0.066, GIST P-value = 0.04 in the replication sample	rs1457466 in the gene desert was marginally associated in th...... rs1457466 in the gene desert was marginally associated in the replication sample by FBAT. It was also associated by GIST, although the opposite allele that was correlated with linkage was found to be overtransmitted by FBAT. More...	Positive
rs2945733	ST3GAL1	A/C		FBAT P-value = 0.001, GIST P-value = 0.05 under recessive model in the initial sample; FBAT P-value = 0.428, GIST P-value > 0.05 in the replication sample	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT and it was identified associated at P<0.05 by using GIST in the initial sample, More...	Positive
rs1870126	ST3GAL1	G/A		FBAT P-value = 0.008, GIST P-value = 0.03 under dominant model in the initial sample; FBAT P-value = 0.241, GIST P-value > 0.05 in the replication sample	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT, and it was identified associated at P<0.05 by using GIST in the initial sample, More...	Positive
rs4377991	ST3GAL1	A/G		FBAT P-value = 0.007, GIST P-value > 0.05 in the initial sample	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT, More...	Positive
rs2978041	ST3GAL1	A/C		FBAT P-value = 0.043, GIST P-value > 0.05 in the initial sample; FBAT P-value = 0.037, GIST P-value > 0.05 in the replication sample	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT; It was significantly associated in the replication sample by FBAT. More...	Positive
rs939024	ST3GAL1	A/G		FBAT P-value = 0.005, GIST P-value > 0.05 in the initial sample; FBAT P-value = 0.517, GIST P-value > 0.05 in the replication sample	It is nominally (P<0.05) significant in the single SNP analy...... It is nominally (P<0.05) significant in the single SNP analysis by FBAT and HBAT, More...	Positive
rs765847	ST3GAL1	G/A		FBAT P-value = 0.008, GIST P-value = 0.0414 under dominant model in the initial sample; FBAT P-value = 0.249, GIST P-value > 0.05 in the replication sample	It was identified associated at P<0.05 by using GIST in the ...... It was identified associated at P<0.05 by using GIST in the initial sample, More...	Positive

Haplotypes reported by this study for BD (count: 3)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs2945733 - rs2978033 - rs1554325		ST3GAL1	P-value = 0.0009	a three-SNP haplotype in the 5' region of ST3GAL1 (rs2945733...... a three-SNP haplotype in the 5' region of ST3GAL1 (rs2945733-rs2978033-rs1554325) was associated at P=0.0009 More...	Positive
rs2673555 - rs1901090		KCNQ3	P-value = 0.003	A two-SNP haplotype in KCNQ3 (rs2673555-rs1901090) was assoc...... A two-SNP haplotype in KCNQ3 (rs2673555-rs1901090) was associated at P=0.003 More...	Positive
rs1457485 - rs4377991 - rs1870126 - rs765847		ST3GAL1	P-value = 0.003	a four-SNP haplotype in the gene desert (rs1457485-rs4377991...... a four-SNP haplotype in the gene desert (rs1457485-rs4377991-rs1870126-rs765847) was associated at P=0.003 More...	Positive

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

Gene	Statistical Values/Author Comments	Result Category
ST3GAL1	Both the single SNP analysis and the haplotype analysis indicated its association with BP. Both the single SNP analysis and the haplotype analysis indicated its association with BP.	Positive
KCNQ3	rs1901090 in the KCNQ3 gene was nominally (P<0.05) significant in the single SNP analysis. A two-...... rs1901090 in the KCNQ3 gene was nominally (P<0.05) significant in the single SNP analysis. A two-SNP haplotype in KCNQ3 (rs2673555-rs1901090) was associated at P=0.003. More...	Positive