Study Report

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Basic Info

Reference	Iwayama, Y., 2010 PMID: 19554614
Citation	Iwayama, Y., E. Hattori, et al. (2010). "Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder." Am J Med Genet B Neuropsychiatr Genet 153B(2): 484-493.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	950 unrelated patients with schizophrenia and 950 controls; 867 unrelated bipolar patients and 895 age- and sex-matched controls.
SNP/Region/Marker Size	16 tag SNPs for FABP7 gene and 8 tag SNPs for FABP3 gene from all SNPs detected by re-sequencing and from SNPs located from the 10kb up- and down-stream regions of the gene [the HapMap data for the Japanese population]
Predominant Ethnicity	Mongloid
Population	Japanese
Gender	For schizophrenia cases, 447 men, 503 women; for schizophrenia controls, 447 men, 503 women; for bipolar disorder cases, 425 men, 442 women; for bipolar disorder controls, 445 men, 450 women.
Age Group	adult : For schizophrenia cases, mean age 47.0(SD=13.7) years; for schizophrenia controls, mean age 46.9(SD=13.6) years; for bipolar disorder cases, mean age 50.7(SD=14.2) years; for bipolar disorder controls, mean age 49.9(SD=13.5) years.

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	Little effect of population stratification was detected by principal components analysis in both schizophrenia and bipolar disorder cases. Control subjects were recruited from hospital staff and volunteers who showed no present or past evidence of psychoses, during brief interviews by psychiatrists.
Technique	Sequencing was performed using the BigDye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems, Foster City, CA) and the ABI PRISM 3730 Genetic Analyzer (Applied Biosystems). Polymorphisms were detected by the SEQUENCHER program (Gene Codes Corporation, Ann Arbor, MI). SNP genotyping was performed using the TaqMan system (Applied Biosystems, Foster City, CA) according to the recommendations of the manufacturer. PCR was performed using an ABI 9700 thermocycler and fluorescent signals were analyzed using an ABI 7900 sequence detector single point measurement and SDS v2.3 software (Applied Biosystems). We tested to confirm the existence of CNPs in Japanese subjects using genomic quantitative PCR.
Statistical Method	Deviations from Hardy-Weinberg equilibrium (HWE) were evaluated by the chi-square test (df=1). Allele and genotype distributions between patients and controls were compared using Fisher's exact test. The Haploview program is used to determine the LD. Haplotype frequency calculations and haplotypic association analyses were performed using the expectation-maximization algorithm implemented in the COCAPHASE program in the UNPHASED v3.0.11 program. Statistical power for detecting association was calculated using the Genetic Power Calculator. Permutation analysis was performed for correction of multiple testing, using the Haploview software.
Result Summary	Three single nucleotide polymorphisms (SNPs) from FABP7 showed nominal association with bipolar disorder, and haplotypes of the same gene showed empirical associations with bipolar disorder even after correction of multiple testing. We could not perform association studies on FABP5, due to the lack of informative SNPs. FABP3 displayed no association with either disease.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 22)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs9490550	FABP7	T/G		P-value for allele test is 0.0636, p-value for genotype test is 0.1713, p-value is 0.6244 after correction by permutation test.		Negative
rs11436	FABP3 ZCCHC17	A/G		allele test P-value = 0.7863, genotype test P-value = 0.9539	None of the 8 SNPs showed association with bipolar disorder None of the 8 SNPs showed association with bipolar disorder	Negative
rs12562824	FABP3	T/C		allele test P-value = 0.0819, genotype test P-value = 0.1922	None of the 8 SNPs showed association with bipolar disorder None of the 8 SNPs showed association with bipolar disorder	Negative
rs12662030	FABP7	A/C		P-value for allele test is 0.0928, p-value for genotype test is 0.2393, p-value is 0.8168 after correction by permutation test.		Negative
rs2279381	FABP7	T/C		P-value for allele test is 0.4937, p-value for genotype test is 0.4869, p-value is 0.9998 after correction by permutation test.		Negative
rs10914367	FABP3	T/C		allele test P-value = 0.4973, genotype test P-value = 0.7251	None of the 8 SNPs showed association with bipolar disorder None of the 8 SNPs showed association with bipolar disorder	Negative
rs6663779	FABP3 ZCCHC17	A/G		allele test P-value = 0.9239, genotype test P-value = 1	None of the 8 SNPs showed association with bipolar disorder None of the 8 SNPs showed association with bipolar disorder	Negative
rs6425744	FABP3	T/C		allele test P-value = 0.2114, genotype test P-value = 0.3406	None of the 8 SNPs showed association with bipolar disorder None of the 8 SNPs showed association with bipolar disorder	Negative
rs6904500	FABP7 SMPDL3A	T/C		P-value for allele test is 0.209, p-value for genotype test is 0.4068, p-value is 0.9648 after correction by permutation test.		Negative
rs6899351	FABP7 SMPDL3A	T/C		P-value for allele test is 0.6507, p-value for genotype test is 0.9025, p-value is 1 after correction by permutation test.		Negative
rs3766293	FABP3 ZCCHC17	A/C		allele test P-value = 0.1916, genotype test P-value = 0.2176	None of the 8 SNPs showed association with bipolar disorder None of the 8 SNPs showed association with bipolar disorder	Negative
rs2279382	FABP7	T/G	G	P-value for allele test is 0.0099, p-value for genotype test is 0.0174, p-value is 0.1544 after correction by permutation test.	showed nominal associations (P<0.05). However, after correct...... showed nominal associations (P<0.05). However, after correction by permutation tests, none remained significant. More...	Positive
rs4247671	FABP7	A/G		P-value for allele test is 0.3693, p-value for genotype test is 0.2028, p-value is 0.9979 after correction by permutation test.		Negative
rs3795432	ZCCHC17 FABP3	A/G		allele test P-value = 0.3517, genotype test P-value = 0.2734	None of the 8 SNPs showed association with bipolar disorder None of the 8 SNPs showed association with bipolar disorder	Negative
rs9401595	FABP7	A/G	G	P-value for allele test is 0.0077, p-value for genotype test is 0.0093, p-value is 0.1165 after correction by permutation test.	showed nominal associations (P<0.05). However, after correct...... showed nominal associations (P<0.05). However, after correction by permutation tests, none remained significant. More...	Positive
rs9401594	FABP7	T/C		P-value for allele test is 0.3594, p-value for genotype test is 0.6554, p-value is 0.9976 after correction by permutation test.		Negative
rs9482286	FABP7 SMPDL3A	T/C		P-value for allele test is 0.4563, p-value for genotype test is 0.7505, p-value is 0.9996 after correction by permutation test.		Negative
rs9401596	FABP7	A/G		P-value for allele test is 0.3081, p-value for genotype test is 0.5911, p-value is 0.9955 after correction by permutation test.		Negative
rs7532813	ZCCHC17 FABP3	G/C		allele test P-value = 0.5189, genotype test P-value = 0.7491	None of the 8 SNPs showed association with bipolar disorder None of the 8 SNPs showed association with bipolar disorder	Negative
rs6919681	FABP7 SMPDL3A	A/G		P-value for allele test is 0.4168, p-value for genotype test is 0.594, p-value is 0.9992 after correction by permutation test.		Negative
rs9372716	FABP7	T/C	T	P-value for allele test is 0.0474, p-value for genotype test is 0.0236, p-value is 0.55 after correction by permutation test.	showed nominal associations (P<0.05). However, after correct...... showed nominal associations (P<0.05). However, after correction by permutation tests, none remained significant. More...	Positive
rs7752838	FABP7	A/G		P-value for allele test is 0.8864, p-value for genotype test is 0.8239, p-value is 1 after correction by permutation test.		Negative

Haplotypes reported by this study for BD (count: 15)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs9490550 - rs9401596	GG	FABP7	P-value = 0.012, global P-value = 0.0352, Permutation global P-value = 0.0332, OR(95% CI)=1.18(1.04-1.35).	is over-represented in the disease group and even after corr...... is over-represented in the disease group and even after correction for multiple testing by permutation tests. More...	Positive
rs4247671 - rs12662030 - rs9372716	GAC	FABP7	P-value = 0.321, global P-value = 0.1940		Negative
rs4247671 - rs12662030 - rs9372716	ACC	FABP7	P-value = 0.099, global P-value = 0.1940		Negative
rs6899351 - rs6919681 - rs6904500	TAC	FABP7	P-value = 0.577, global P-value = 0.5686		Negative
rs6899351 - rs6919681 - rs6904500	TAT	FABP7	P-value = 0.219, global P-value = 0.5686		Negative
rs6899351 - rs6919681 - rs6904500	CGC	FABP7	P-value = 0.741, global P-value = 0.5686		Negative
rs6899351 - rs6919681 - rs6904500	TGC	FABP7	P-value = 0.334, global P-value = 0.5686		Negative
rs9490550 - rs9401596	GA	FABP7	P-value = 0.313, global P-value = 0.0352, Permutation global P-value = 0.0332		Negative
rs9490550 - rs9401596	TG	FABP7	P-value = 0.057, global P-value = 0.0352, Permutation global P-value = 0.0332		Negative
rs2279382 - rs2279381 - rs7752838	TCG	FABP7	P-value = 0.009, global P-value = 0.0322, Permutation global P-value = 0.0323, OR (95% CI)=0.82(0.71-0.95)	is over-represented in the control group and even after corr...... is over-represented in the control group and even after correction for multiple testing by permutation tests. More...	Positive
rs2279382 - rs2279381 - rs7752838	TCA	FABP7	P-value = 0.902, global P-value = 0.0322, Permutation global P-value = 0.0323		Negative
rs2279382 - rs2279381 - rs7752838	GCG	FABP7	P-value = 0.017, global P-value = 0.0322, Permutation global P-value = 0.0323, OR(95% CI)=1.19(1.03-1.36)	is over-represented in the disease group and even after corr...... is over-represented in the disease group and even after correction for multiple testing by permutation tests. More...	Positive
rs2279382 - rs2279381 - rs7752838	GTG	FABP7	P-value = 0.546, global P-value = 0.0322, Permutation global P-value = 0.0323		Negative
rs4247671 - rs12662030 - rs9372716	AAC	FABP7	P-value = 0.988, global P-value = 0.1940		Negative
rs4247671 - rs12662030 - rs9372716	AAT	FABP7	P-value = 0.047, global P-value = 0.1940		Positive

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

Gene	Statistical Values/Author Comments	Result Category
FABP7	Three single nucleotide polymorphisms (SNPs) from FABP7 showed nominal association with bipolar diso...... Three single nucleotide polymorphisms (SNPs) from FABP7 showed nominal association with bipolar disorder, and haplotypes of the same gene showed empirical associations with bipolar disorder even after correction of multiple testing. More...	Positive
FABP3	FABP3 displayed no association with bipolar disorder. FABP3 displayed no association with bipolar disorder.	Negative

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	rs10914367	FABP3	allele test P-value = 0.7429, genotype test P-value = 0.6223	None of the 8 SNPs showed association with schizophrenia.	Negative
SZ	rs11436	FABP3 ZCCHC17	allele test P-value = 0.3073, genotype test P-value = 0.4655	None of the 8 SNPs showed association with schizophrenia.	Negative
SZ	rs12562824	FABP3	allele test P-value = 0.8354, genotype test P-value = 0.6886	None of the 8 SNPs showed association with schizophrenia.	Negative
SZ	rs3766293	FABP3 ZCCHC17	allele test P-value = 0.058, genotype test P-value = 0.139	None of the 8 SNPs showed association with schizophrenia.	Negative
SZ	rs3795432	ZCCHC17 FABP3	allele test P-value = 0.2038, genotype test P-value = 0.4391	None of the 8 SNPs showed association with schizophrenia.	Negative
SZ	rs6425744	FABP3	allele test P-value = 0.6259, genotype test P-value = 0.2468	None of the 8 SNPs showed association with schizophrenia.	Negative
SZ	rs6663779	FABP3 ZCCHC17	allele test P-value = 0.8552, genotype test P-value = 0.8512	None of the 8 SNPs showed association with schizophrenia.	Negative
SZ	rs7532813	ZCCHC17 FABP3	allele test P-value = 0.6697, genotype test P-value = 0.5818	None of the 8 SNPs showed association with schizophrenia.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	FABP3	FABP3 displayed no association with schizophrenia.	Negative