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	Squassina, A.,2008 PMID: 18496210
Citation	Squassina, A., M. Manchia, et al. (2008). "A case-control association study of the PDLIM5 gene and bipolar disorder in a Sardinian sample." Psychiatr Genet 18(3): 128-132.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	300 BD and 300 controls
SNP/Region/Marker Size	3 SNPs
Predominant Ethnicity	Caucasian
Population	Italian
Gender	BD patients (110 males and 190 females), healthy controls (140 males and 160 females)
Age Group	BD patients: mean age=42.9 (SD=13.8) years; healthy controls: mean age=42.2 (SD=12) years,

Detail Info

Sample Diagnosis	Research Diagnostic Criteria
Sample Status	Mean age at onset, the time in life when manic or depressive symptoms first occurred, was 25.8 years (SD=10.2).
Technique	PCR and genotyping
Statistical Method	Deviation from the Hardy-Weinberg equilibrium was examined in cases and controls by X² test. Linkage disequilibrium (LD) between markers was estimated by the standardized Lewontin coefficient (D') and squared correlation (r²). Allelic and genotypic distributions in cases and controls were compared using the X² and Fisher's exact tests. Haplotype frequencies were estimated by means of the expectation-maximization algorithm. Rare haplotypes with frequency lower than 0.01 were dropped. We carried out a permutation test with 10 000 permutations for evaluating the possible contribution of individual haplotypes to any deviation from the null hypothesis of no association and to obtain a significance value of the applied X² statistics corrected for multiple comparisons. Statistical tests were carried out using Haploview version 4.0 and Unphased version 3.09. Power analysis was calculated using the 'Power and Sample Size Calculation' program, version 2.1.30. Presuming a frequency of 40% for the risk allele and alpha value of 0.05, our sample had over 80% power to detect association for a susceptibility marker with an odds ratio (OR) of 1.6.
Result Summary	In single-marker analysis, no association was found for any of the SNPs tested. After correction for multiple testing, haplotype analysis showed slight statistically significant association for a rare haplotype of SNPs 1 and 2. Although the findings presented in this paper do not provide strong evidence that the PDLIM5 gene significantly affects the pathophysiology of BD, they suggest that rare variants within the promoter region of the gene may have a marginal effect on the disorder. Further investigation on independent samples and different populations is warranted

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs10008257	PDLIM5	A/G		Allelic P-value = 0.202; OR=1.1; genotypic P-value = 0.436	In single-marker analysis, no association was found for any ...... In single-marker analysis, no association was found for any of the SNPs tested. More...	Negative
rs2433320	PDLIM5	A/G		Allelic P-value = 0.261; OR=1.1; genotypic P-value = 0.055	We found an association trend for the genotype GG at this SN...... We found an association trend for the genotype GG at this SNP, with higher frequency in BD than in controls. More...	Negative
rs2433322	PDLIM5	A/G		Allelic P-value = 0.288; OR=1.1; genotypic P-value = 0.068	In single-marker analysis, no association was found for any ...... In single-marker analysis, no association was found for any of the SNPs tested. More...	Negative

Haplotypes reported by this study for BD (count: 13)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs10008257 - rs2433320		PDLIM5	Global P-value = 0.025	We found weak association for haplotypes of SNP1-SNP2. Not s...... We found weak association for haplotypes of SNP1-SNP2. Not significant after correction for multiple comparisons. More...	Positive
rs10008257 - rs2433320	A-G	PDLIM5	X<sup>2</sup>=0.49; P-value = 0.48		Negative
rs10008257 - rs2433320	A-A	PDLIM5	X<sup>2</sup>=3.96; P-value = 0.047	Not significant after correction for multiple comparisons. Not significant after correction for multiple comparisons.	Negative
rs10008257 - rs2433320	G-G	PDLIM5	X<sup>2</sup>=0.34; P-value = 0.56		Negative
rs10008257 - rs2433320	G-A	PDLIM5	X<sup>2</sup>=6.84; P-value = 0.009; corrected P-value = 0.040 after permutation test (10 000 permutations).	The most significant P value was obtained for the rare haplo...... The most significant P value was obtained for the rare haplotype G-A of SNPs 1 and 2. More...	Positive
rs10008257 - rs2433320 - rs2433322	A-A-G	PDLIM5	X<sup>2</sup>=3.98; P-value = 0.047	The most common haplotype A-A-G was more highly represented ...... The most common haplotype A-A-G was more highly represented in the control group. More...	Negative
rs10008257 - rs2433320 - rs2433322		PDLIM5	Global P-value = 0.033	Haplotype analysis showed slight statistical association for...... Haplotype analysis showed slight statistical association for the three SNP haplotypes. Not significant after correction for multiple comparisons. More...	Positive
rs10008257 - rs2433320 - rs2433322	G-A-G	PDLIM5	X<sup>2</sup>=5.94; P-value = 0.013	Not significant after correction for multiple comparisons. T...... Not significant after correction for multiple comparisons. The rare haplotype G-A-G was more frequent in the BD group. More...	Positive
rs10008257 - rs2433320 - rs2433322	A-G-A	PDLIM5	X<sup>2</sup>=0.39; P-value = 0.54		Negative
rs2433320 - rs2433322		PDLIM5	Global P-value = 0.255	No association was found No association was found	Negative
rs10008257 - rs2433320 - rs2433322	G-G-A	PDLIM5	X<sup>2</sup>=0.34; P-value = 0.56		Negative
rs2433320 - rs2433322	G-A	PDLIM5	X<sup>2</sup>=1.18; P-value = 0.28		Negative
rs2433320 - rs2433322	A-G	PDLIM5	X<sup>2</sup>=1.45; P-value = 0.23		Negative

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

Gene	Statistical Values/Author Comments	Result Category
PDLIM5	In single-marker analysis, no association was found for any of the SNPs tested. After correction for multiple testing, haplotype analysis showed slight statistically significant association for a rare haplotype of SNPs 1 and 2, P-value = 0.009; corrected P-value = 0.040 . Although the findings presented in this paper do not provide strong evidence that the PDLIM5 gene si...... Although the findings presented in this paper do not provide strong evidence that the PDLIM5 gene significantly affects the pathophysiology of BD, they suggest that rare variants within the promoter region of the gene may have a marginal effect on the disorder. More...	Positive