Study Report

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Basic Info

Reference	Kahler, A. K., 2010 PMID: 19350560
Citation	Kahler, A. K., M. K. Otnaess, et al. (2010). "Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples." Am J Med Genet B Neuropsychiatr Genet 153B(1): 86-96.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	837 SZ cases and 1,473 controls plus 594 BP cases and 1,421 partly overlapping controls. A subset of Norwegian SZ patients (n=153; 54.2% men, 45.8% women), and BP patients (n=128; 39.8% men, 60.2% women), were symptomatically evaluated with the Positive And Negative Syndrome Scale (PANSS).
SNP/Region/Marker Size	44 and 76 tagSNPs for SZ and BP respectively.
Predominant Ethnicity	Caucasian
Population	Norway, Sweden, and Denmark for SZ sample; Norway and Denmark for BD sample.

Detail Info

Sample Diagnosis	DSM-IV using Structural Clinical Interview for DSM-IV (SCID), ICD-10, DSM-III-R/DSM-IV, ICD-10-DCR and SCAN interviews were used for different group of sample.
Sample Status	734 SZ, 87 schizoaffective disorder and 16 schizophreniform disorder (SZPH) cases for SZ sample; The Norwegian patients had been diagnosed with bipolar disorder type I (BPI) (n=125), bipolar disorder type II (BPII) (n=80), and BP not otherwise specified (NOS) (n=13), according to DSM-IV using SCID.
Technique	genopying using the GoldenGate 1536plex assay (Illumina, Inc., San Diego, CA) on the Illumina BeadStation 500GX at the SNP Technology Platform, Uppsala University, Sweden (www.genotyping.se), accredited by the Swedish accreditation agency SWEDAC, and approved according to a quality system based on the international SS-EN ISO/IEC 17025 standard.
Statistical Method	PLINK for HWD test, calculate the gene based F_ST for PDE4B, in both the SZ and BP control sample sets, as implemented in Arlequin 3.1. Allelic and genotypic single SNP association tests, as well as a sliding-window haplotype analysis, were performed with UNPHASED (version 3.0.13). Pairwise LD (D' and r²) and LD blocks were estimated in Haploview 4.1. Also, ORs for the risk allele and the individual genotypes with the largest effect size were determined in each population separately, using UNPHASED. The genotype-phenotype association analysis was performed using the non-parametric Kruskal-Wallis test, implemented in SPSS (version 16.0) for PANSS sample.
Result Summary	Six and 16 tagSNPs were nominally associated (0.0005 < P < 0.05) with SZ and BP, respectively, in the combined samples or in gender-specific subgroups. None of these findings remained significant after correction for multiple testing. Four tagSNPs were associated with SZ in women, but none in men. Proxies of two nominally associated SNPs in the SZ sample were also associated with BP. Finally, four SNPs were found to be associated with Positive And Negative Syndrome Scale (PANSS) positive symptom scores in a subgroup of SZ patients (n=153) or SZ female patients (n=70).

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 16)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs12142070	PDE4B		T	genotype test: P-value = 0.0049 in males, allele test: OR=1.07 in males, OR=1.2 in Demark males, OR=0.81 in Normay males.	nominally significant only in males. nominally significant only in males.	Positive
rs12731764	PDE4B	G/G	A	genotype test: P-value = 0.016, allele test: P-value = and OR=1.02 for all samples, OR=1.11 in Denmark samples, OR=1.17 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing. None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs12080701	PDE4B	G/G	G	genotype test: P-value = 0.019, allele test: P-value = 0.059 and OR=1.24(1.00-1.55) for all samples, OR=1.26 in Denmark samples, OR=1.2 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing. None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs12140107	PDE4B	A/G	A	genotype test: P-value = 0.008, allele test: P-value = 0.023 and OR=1.27(1.03-1.56) for all samples, P-value = 0.042 and OR=1.29(1.00-1.66) in Denmark samples, OR=1.22 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing. None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs11208793	PDE4B		T	genotype test: P-value = 0.076 in females, allele test: P-value = 0.046 and OR=1.23(1.00-1.50) in females, OR=1.14 in Demark females, P-value = 0.045 and OR=1.48(1.01-2.18) in Normay females.	nominally significant only in females. nominally significant only in females.	Positive
rs11208816	PDE4B		T	genotype test: P-value = 0.017 in males, allele test: P-value = 0.008 and OR=1.33 in males, P-value = 0.006 and OR=1.41 in Demark males, OR=1.13 in Normay males.	nominally significant only in males. nominally significant only in males.	Positive
rs11208776	PDE4B	A/A	A	allele test: P-value = 0.045 and OR=1.15(1.00-1.33) for all samples, OR=1.1 in Denmark samples, P-value = 0.043 and OR=1.32(1.02-1.71) in Normay samples. P_{positive score}=0.14, P_{negative score}=0.017 and P_adjusted=0.24 for PANSS score test results.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing.None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs6421482	PDE4B		A	allele test: P-value = 0.047 and OR=1.15(1.00-1.33) for all samples, OR=1.14 in Denmark samples, OR=1.2 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing.None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs7415930	PDE4B		T	genotype test: P-value = 0.040 in males, allele test: P-value = 0.084 and OR=1.29 in males, OR=1.28 in Demark males, OR=1.32 in Normay males.	nominally significant only in males. nominally significant only in males.	Positive
rs2186122	PDE4B	A/A	A	genotype test: P-value = 0.053, allele test: P-value = 0.017 and OR=1.19(1.03-1.37) for all samples, P-value = 0.053 and OR=1.18 in Denmark samples, OR=1.22 in Normay samples. P_{positive score}=0.33 and P_{negative score}=0.051 for PANSS score test results.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing.None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs522037	PDE4B	C/G	G	genotype test: P-value = 0.047, allele test: P-value = and OR=1.07 for all samples, OR=1.04 in Denmark samples, OR=1.15 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing. None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs1937451	PDE4B	T/T	T	genotype test: P-value = 0.042, allele test: P-value = 0.034 and OR=1.22(1.02-1.47) for all samples, OR=1.2 in Denmark samples, OR=1.3 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing.None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs2144719	PDE4B	T/G	T	genotype test: P-value = 0.044, allele test: P-value = and OR=1.02 for all samples, OR=1.03 in Denmark samples, OR=1.02 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing. None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs17424885	PDE4B		G	genotype test: P-value = 0.038 in females, allele test: P-value = 0.038 and OR=1.33(1.01-1.75) in females, OR=1.28 in Demark females, OR=1.45 in Normay females.	nominally significant only in females. nominally significant only in females.	Positive
rs17452121	PDE4B	G/G	G	genotype test: P-value = 0.005, allele test: P-value = 0.049 and OR=1.27(1.01-1.60) for all samples, P-value = 0.051 and OR=1.31(1.02-1.69) in Denmark samples, OR=1.15 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing.None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP sample. More...	Positive
rs7552762	PDE4B	G/G	G	genotype test: P-value = 0.02, allele test: P-value = 0.059 and OR=1.24(1.00-1.55) for all samples, OR=1.25 in Denmark samples, OR=1.21 in Normay samples.	nominally significant in allele- or genotype-based tests, no...... nominally significant in allele- or genotype-based tests, none of the tagSNPs remained significantly associated with BP after correction for multiple testing. None of the tagSNPs nominally associated with BP were associated with positive or negative symptoms in the BP 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
rs937605 - rs524897	CT	PDE4B	individual P-value = 0.0056, OR(95% CI)=1.93(1.24-2.99), global P-value = 0.035	the strongest nominally associated the strongest nominally associated	Positive
rs17452121 - rs2186122	AT	PDE4B	Individual P-value = 0.010, global P-value = 0.030	the best 2-SNP result the best 2-SNP result	Positive
rs558325 - rs1040716 - rs11803904 - rs12142015		PDE4B	global P-value = 0.0057	the best overall 4-SNP result, but none of the individual ha...... the best overall 4-SNP result, but none of the individual haplotypes displayed association with disease More...	Positive

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

Gene	Statistical Values/Author Comments	Result Category
PDE4B	nominal associations were found between PDE4B markers and BP in this study nominal associations were found between PDE4B markers and BP in this study	Positive

Genetic factors reported by this study for SZ and/or MDD

SNPs reported by this study for SZ/MDD

Disease	SNP	Related Gene(s)	Statistical Values	Description	Result Category
SZ	rs11208776	PDE4B	LD-proxy of rs11208776 (rs1937450): genotype test: P-value = 0.046 in females, allele test: P-value = 0.032 and OR=1.23(1.02-1.49) in females, P-value = 0.067 and OR=1.26 in Demark females, OR=1.29 in Normay females, OR=1.11 in Sweden females.	LD-proxy of rs11208776 (rs1937450) is nominally associated with SZ in females.	Positive
SZ	rs2186122	PDE4B	LD-proxy of rs2186122 (rs3009872): genotype test: P-value = 0.043 in females, allele test: P-value = 0.088 and OR=1.18 in females, OR=1.14 in Demark females, OR=1.35 in Normay females, OR=1.15 in Sweden females.	LD-proxy of rs2186122 (rs3009872) is nominally associated with SZ in females.	Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	PDE4B	nominal associations were found between PDE4B markers and SZ in this study	Positive