Study Report

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Basic Info

Reference	Abou Jamra, R, 2008 (a) PMID: 17938632
Citation	Abou Jamra, R., T. Becker, et al. (2008). "Genetic variation of the FAT gene at 4q35 is associated with bipolar affective disorder." Mol Psychiatry 13(3): 277-284.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	425 BD and 419 controls
SNP/Region/Marker Size	48 SNPs
Predominant Ethnicity	Caucasian
Population	German
Gender	425 BD patients (52.7% female and 47.3% male). 419 controls (44.6% female and 55.4% male)
Age Group	adults : BD patients: mean age=43.6 (SD=10.9) years; controls: mean age=48.4 (SD=15.6) years

Detail Info

Sample Diagnosis	A comprehensive inventory for phenotype characterization-IPGS, This included a SCID-I Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition and the OPCRIT system as well as a review of medical records
Sample Status	We subdivided the sample according to the presence of a positive family history of psychiatric illness in first and second degree relatives (FH, n = 290), a lifetime history of psychotic symptoms (Psych, n = 272), a lifetime history of persecutory delusions (PerDel, n = 157), and an early age of onset ( < 21 years, n = 126)
Technique	Illumina's Golden Gate Assays
Statistical Method	Departure from Hardy-Weinberg equilibrium was tested using a X²-test (1 d.f.). Single-marker association analysis was performed using the Cochrane- Armitage trend test. Power calculations were conducted using the Genetic Power Calculator.Haplotype distributions in patients and controls were compared using FAMHAP. All marker combinations were tested by comparing haplotype frequency distribution between patients and controls for all possible marker combinations. For each marker combination, a global P-value, corrected for multiple testing, was computed using Monte-Carlo simulations.
Result Summary	No significant association was observed for SNPs located in the MTNR1A gene. In FAT, however, nine SNPs showed association, eight of them being located in the same haplotype block found to be associated with BPAD by Blair et al. The smallest P-value of 0.00028 (OR 1.71) was seen for nonsynonymous SNP rs2637777. A combination of five markers including this marker showed a haplotype distribution with a nominal P-value of 1.8 E-05 that withstands correction for multiple testing. While the control allele frequencies between our sample and the samples of the original study are comparable, tendencies of risk allele frequencies are opposite.

SNPs reported by this study for BD (count: 48)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs455219	FAT1 CD36	A/G	allelic P-value = 0.26314	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs459796	FAT1 CD36	A/T	allelic P-value = 0.67832	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs4861722	MTNR1A	A/G	allelic P-value = 0.49996	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs4862706	MTNR1A	A/G	allelic P-value = 0.76394	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs328438	FAT1 CD36	C/T	allelic P-value = 0.79878	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs3733413	FAT1 CD36	C/T	allelic P-value = 0.41296	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs3733414	FAT1 CD36	A/C	allelic P-value = 0.41184	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs4241833	CD36	C/G	allelic P-value = 0.25435	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs6553010	MTNR1A	A/G	allelic P-value = 0.11033	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs6553013	MTNR1A	C/T	allelic P-value = 0.65143	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs6818461	FAT1 CD36	A/G	allelic P-value = 0.23573	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs6820205	MTNR1A	C/T	allelic P-value = 0.61779	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs4862709	MTNR1A	A/G	allelic P-value = 0.87247	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs4862711	MTNR1A	A/G	allelic P-value = 0.68419	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs4862717	CD36	A/G	allelic P-value = 0.19232	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs4862718	CD36	C/T	allelic P-value = 0.02786; OR=1.31	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs2584345	FAT1 CD36	C/T	allelic P-value = 0.17125	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs2306990	FAT1 CD36	C/T	allelic P-value = 0.00248; OR=1.59	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs327070	FAT1 CD36	G/T	allelic P-value = 0.61467	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs2637777	FAT1 CD36	G/T	allelic P-value = 0.00028; OR=1.71	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs2249917	FAT1 CD36	C/T	allelic P-value = 0.07175	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs2165668	MTNR1A	C/T	allelic P-value = 0.41454	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs2306987	FAT1 CD36	A/T	allelic P-value = 0.02326; OR=1.50	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs2304865	FAT1 CD36	C/G	allelic P-value = 0.03737; OR=1.36	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs327102	FAT1 CD36	A/G	allelic P-value = 0.62242	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs327095	FAT1 CD36	G/T	allelic P-value = 0.4988	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs328437	FAT1 CD36	G/T	allelic P-value = 0.01417; OR=3.35	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs328429	FAT1 CD36	C/T	allelic P-value = 0.30121	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs327078	FAT1 CD36	C/G	allelic P-value = 0.41449	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs327077	FAT1 CD36	A/G	allelic P-value = 0.41449	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs327080	FAT1 CD36	C/T	allelic P-value = 0.9544	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs327079	FAT1 CD36	C/T	allelic P-value = 0.21822	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs10009030	FAT1 CD36	A/C	allelic P-value = 0.01498; OR=1.50	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs11721818	MTNR1A	A/T	allelic P-value = 0.73283	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs10008039	FAT1 CD36	A/G	allelic P-value = 0.92812	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs1300054	FAT1 CD36	A/G	allelic P-value = 0.9525	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs13113549	MTNR1A	A/G	allelic P-value = 0.51903	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs11724817	FAT1 CD36	A/T	allelic P-value = 0.63848	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs1298865	FAT1 CD36	A/G	allelic P-value = 0.00079; OR=1.69	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs1946979	MTNR1A	G/T	allelic P-value = 0.42703	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs2119882	MTNR1A	C/T	allelic P-value = 0.69798	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs13140444	MTNR1A	C/T	allelic P-value = 0.72334	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs1946977	MTNR1A	G/T	allelic P-value = 0.77019	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs9991886	FAT1 CD36	C/T	allelic P-value = 0.07971	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs997696	FAT1 CD36	C/G	allelic P-value = 0.7144	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative
rs7683023	CD36	C/T	allelic P-value = 0.01164; OR=1.34	showed association with bipolar affective disorder showed association with bipolar affective disorder	Positive
rs7665239	MTNR1A	A/T	allelic P-value = 0.64365	In the single-marker analysis, none of the 15 MTNR1A SNPs sh...... In the single-marker analysis, none of the 15 MTNR1A SNPs showed significant evidence of association with bipolar affective disorder. More...	Negative
rs7663350	FAT1 CD36	C/T	allelic P-value = 0.2655	showed no association with bipolar affective disorder showed no association with bipolar affective disorder	Negative

Haplotypes reported by this study for BD (count: 4)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs2306987 - rs1298865 - rs10009030 - rs2637777 - rs2304865	TGCGG	CD36	haplotype TGCGG (3 vs 1% in controls) and shows a P-value = 0.003, OR= 2.04)	The less frequent haplotype TGCGG is significantly overrepre...... The less frequent haplotype TGCGG is significantly overrepresented in patients. More...	Positive
rs2306987 - rs1298865 - rs10009030 - rs2637777 - rs2304865	TACTG	CD36	haplotype TACTG (59 vs 66% in controls, P-value of 0.001, OR of 0.72).	The opposite haplotype, TACTG, is significantly underreprese...... The opposite haplotype, TACTG, is significantly underrepresented in the patients. More...	Positive
rs2306987 - rs1298865 - rs10009030 - rs2637777 - rs2304865	AGAGC	CD36	haplotype AGAGC (35 vs 30% in controls, P-value = 0.029, OR= 1.62).	Haplotype AGAGC is overrepresented in patients. Haplotype AGAGC is overrepresented in patients.	Positive
rs2306987 - rs1298865 - rs10009030 - rs2637777 - rs2304865		CD36	global P-value = 0.000018 (0.00028 after correction for multiple testing of all marker combinations of the block according to Becker et al.).		Positive

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

Gene	Statistical Values/Author Comments	Result Category
MTNR1A	No significant association was observed for SNPs located in the MTNR1A gene No significant association was observed for SNPs located in the MTNR1A gene	Negative
CD36	In FAT, nine SNPs showed association, eight of them being located in the same haplotype block found ...... In FAT, nine SNPs showed association, eight of them being located in the same haplotype block found to be associated with bipolar affective disorder (BPAD) by Blair et al. More...	Positive