Study Report

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Basic Info

Reference	Ram Murthy, A., 2012 PMID: 22673686
Citation	Ram Murthy, A., M. Purushottam, et al. (2012). "Gender-specific association of TSNAX/DISC1 locus for schizophrenia and bipolar affective disorder in South Indian population." J Hum Genet 57(8): 523-530.
Disease Type	bipolar affective disorder & schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	419 patients with BPAD type I, 408 patients with SCZ and 425 controls
SNP/Region/Marker Size	7 SNPs
Predominant Ethnicity
Population	Indian
Gender	225 males and 194 females with BPAD type I, 246 males and 162 females with SCZ, 243 males and 182 females controls
Age Group	adults : mean age at assessment: 29.02, SD=10.98 years of BPAD patients, mean age at assessment: 29.08, SD=7.84 years of SCZ patients, mean age: 33.61, SD=11.15 years of controls

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	The study sample comprised of 419 patients with diagnosis of BPAD type I (mean age at onset: 20.73, SD=6.96 years) and 408 patients with diagnosis of SCZ (mean age at onset: 23.21, SD=7.16 years) recruited from the inpatient and outpatient services of National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India. All patients were evaluated using the Diagnostic Interview for Genetic Studies.
Technique	genotyping using the ABI PRISM SNaPshot Multiplex Kit
Statistical Method	Mann-Whitney test was performed to check for age differences between cases and controls. Allele and genotype frequencies were also compared using standard Chi-square (X2) tests. Haplotype analysis was performed using HAPLOVIEW v 4.0 (Broad Institute, Cambridge, MA, USA), which uses the expectation maximization algorithm to estimate haplotype frequencies. Hardy-Weinberg equilibrium was assessed for all markers using HAPLOVIEW v 4.0. Association tests with p-values < 0.05 were considered to be nominally significant. We corrected for multiple tests using false discovery rate (FDR) approach. We used an overall FDR of 0.05 for our association tests.
Result Summary	Binary logistic regression revealed a nominal association for rs821616 in DISC1 for BPAD and also combined cases of BPAD or SCZ, but after correcting for multiple testing, these results were non-significant. However, significant association was observed with BPAD, as well as combined cases of BPAD or SCZ, within the female subjects for the rs766288 after applying false discovery rate corrections at the 0.05 level. Two-locus analysis showed C-C (rs766288-rs2812393) as a risk combination in BPAD, and G-T (rs2812393-rs821616) as a protective combination in SCZ and combined cases of BPAD or SCZ. Female-specific associations were observed for rs766288-rs2812393, rs766288-rs821616 and rs8212393-rs821616 in two-locus analysis. Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD.

Genetic factors reported by this study for BD

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

SNP	Related Gene(s)	Statistical Values	Author Comments	Result Category
rs2812393	DISC1 TSNAX	BPAD patients: P-value=0.135, P-value=0.122 for females, P-value=0.532 for males; BPAD&SCZ: P-value=0.073, P-value=0.028 for females, P-value=0.668 for males	Moderate associations were also observed in females for rs28...... Moderate associations were also observed in females for rs2812393 (SCZ, P=0.026; BPAD&SCZ, P=0.028). More...	Positive
rs3738401	DISC1 TSNAX	BPAD patients: P-value=0.368, P-value=0.443 for females, P-value=0.0614 for males; BPAD&SCZ: P-value=0.520, P-value=0.875 for females, P-value=0.529 for males		Negative
rs766288	TSNAX DISC1	BPAD patients: P-value=0.074, P-value=0.004 for females, P-value=0.0902 for males; BPAD&SCZ: P-value=0.336, P-value=0.004 for females, P-value=0.248 for males	The most significant association was found for rs766288 with...... The most significant association was found for rs766288 with BPAD females. More...	Positive
rs821616	DISC1 TSNAX	BPAD patients: P-value=0.035, P-value=0.175 for females, P-value=0.112 for males; BPAD&SCZ: P-value=0.04, P-value=0.138 for females, P-value=0.183 for males	One SNP (rs821616) showed moderate significant association w...... One SNP (rs821616) showed moderate significant association with cases compared with controls in regression analysis More...	Positive

Haplotypes reported by this study for BD (count: 14)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs2812393 - rs821616	C-T	DISC1	P-value=0.799 for BPAD, P-value=0.531 for combined cases, P-value=0.752 for BPAD females, P-value=0.642 for combined females, P-value=0.537 for BPAD males, P-value=0.206 for combined males		Negative
rs766288 - rs3738401 - rs2812393 - rs821616	C-G-G-T	TSNAX DISC1	P-value=0.028 for BPAD, P-value=0.074 for BPAD&SZ	C-G-G-T haplotype showed relatively lesser frequency in BPAD...... C-G-G-T haplotype showed relatively lesser frequency in BPAD (P=0.028), SCZ (P=0.0189) and combined cases of BPAD or SCZ (P=0.0065) and combined males of BPAD or SCZ (P=0.0205) compared with controls. More...	Positive
rs766288 - rs821616	C-T	TSNAX DISC1	P-value=0.316 for BPAD, P-value=0.115 for combined cases, P-value=0.835 for BPAD females, P-value=0.489 for combined females, P-value=0.244 for BPAD males, P-value=0.177 for combined males		Negative
rs766288 - rs821616	A-A	TSNAX DISC1	P-value=0.667 for BPAD, P-value=0.831 for combined cases, P-value=0.032 for BPAD females, P-value=0.022 for combined females, P-value=0.187 for BPAD males, P-value=0.028 for combined males	Few additional combinations that were found to be significan...... Few additional combinations that were found to be significantly associated after multiple corrections (n=12) were A-T in BPAD females (P=0.012, protective combination); C-A (P=0.014, risk combination), C-A in SCZ females (P=0.011, risk combination), A-T in combined female cases (P=0.012, protective combination) and A-A in combined female cases (P=0.022, protective combination) compared with control females. However nominal significance observed in BPAD (C-A, P=0.024, risk combination), cases with the combined phenotype (C-A, P=0.019, risk combination), SCZ males (A-A, P=0.016, risk combination) and males with the combined phenotype (A-A, P=0.028, risk combination), which did not withstand the multiple corrections. More...	Positive
rs766288 - rs821616	C-A	TSNAX DISC1	P-value=0.024 for BPAD, P-value=0.019 for combined cases, P-value=0.014 for BPAD females, P-value=0.004 for combined females, P-value=0.413 for BPAD males, P-value=0.589 for combined males	Allelic combination C-A (P=0.004) in the female cases with c...... Allelic combination C-A (P=0.004) in the female cases with combined phenotype showed significant association when multiple corrections were performed for all tests within each stratified gender (combined, females, males). More...	Positive
rs766288 - rs3738401 - rs2812393 - rs821616	A-G-G-T	TSNAX DISC1	P-value=0.0273 for BPAD females, P-value=0.0469 for BPAD&SZ, P-value=0.0209 for BPAD females &SCZ females	Haplotype A-G-G-T was also underrepresented in combined case...... Haplotype A-G-G-T was also underrepresented in combined cases of BPAD or SCZ (P=0.0469), BPAD females (P=0.0273) and pooled females of BPAD or SCZ (P=0.0209). More...	Positive
rs766288 - rs2812393	C-G	TSNAX DISC1	P-value=0.979 for BPAD, P-value=0.703 for combined cases, P-value=0.717 for BPAD females, P-value=0.969 for combined females, P-value=0.764 for BPAD males, P-value=0.672 for combined males		Negative
rs766288 - rs2812393	A-G	TSNAX DISC1	P-value=0.412 for BPAD, P-value=0.551 for combined cases, P-value=0.598 for BPAD females, P-value=0.013 for combined females, P-value=0.057 for BPAD males, P-value=0.212 for combined males	Other combinations in BPAD females (C-C, P=0.003, risk combi...... Other combinations in BPAD females (C-C, P=0.003, risk combination) and SCZ females (C-C, P=0.011, risk combination; A-G, P=0.016, protective combination), combined female cases (A-G, P=0.013, protective combination; C-C, P=0.001, risk combination) were found to be significantly associated after FDR corrections. More...	Positive
rs766288 - rs2812393	C-C	TSNAX DISC1	P-value=0.009 for BPAD, P-value=0.016 for combined cases, P-value=0.003 for BPAD females, P-value=0.001 for combined females, P-value=0.414 for BPAD males, P-value=0.703 for combined males	Analyses of these two SNPs showed significant associations w...... Analyses of these two SNPs showed significant associations with allelic combination C-C (P=0.009) in the BPAD phenotype when multiple corrections were performed for all tests within each stratified gender (combined, females, males). More...	Positive
rs766288 - rs821616	A-T	TSNAX DISC1	P-value=0.114 for BPAD, P-value=0.215 for combined cases, P-value=0.012 for BPAD females, P-value=0.012 for combined females, P-value=0.875 for BPAD males, P-value=0.606 for combined males	Few additional combinations that were found to be significan...... Few additional combinations that were found to be significantly associated after multiple corrections (n=12) were A-T in BPAD females (P=0.012, protective combination); C-A (P=0.014, risk combination), C-A in SCZ females (P=0.011, risk combination), A-T in combined female cases (P=0.012, protective combination) and A-A in combined female cases (P=0.022, protective combination) compared with control females. However nominal significance observed in BPAD (C-A, P=0.024, risk combination), cases with the combined phenotype (C-A, P=0.019, risk combination), SCZ males (A-A, P=0.016, risk combination) and males with the combined phenotype (A-A, P=0.028, risk combination), which did not withstand the multiple corrections. More...	Positive
rs2812393 - rs821616	G-T	DISC1	P-value=0.017 for BPAD, P-value=0.001 for combined cases, P-value=0.035 for BPAD females, P-value=0.005 for combined females, P-value=0.193 for BPAD males, P-value=0.039 for combined males	Allelic combinations of G-T in SCZ (P=0), combined cases of ...... Allelic combinations of G-T in SCZ (P=0), combined cases of BPAD or SCZ (P=0.001), SCZ females (P=0.007) and combined females (P=0.005) were observed to be protective combination of alleles. These combinations survived multiple corrections. In addition allelic combinations of G-T showed nominal significance, but did not withstand FDR corrections. More...	Positive
rs2812393 - rs821616	G-A	DISC1	P-value=0.699 for BPAD, P-value=0.806 for combined cases, P-value=0.729 for BPAD females, P-value=0.834 for combined females, P-value=0.859 for BPAD males, P-value=0.898 for combined males		Negative
rs2812393 - rs821616	C-A	DISC1	P-value=0.088 for BPAD, P-value=0.125 for combined cases, P-value=0.172 for BPAD females, P-value=0.077 for combined females, P-value=0.268 for BPAD males, P-value=0.673 for combined males		Negative
rs766288 - rs2812393	A-C	TSNAX DISC1	P-value=0.897 for BPAD, P-value=0.632 for combined cases, P-value=0.161 for BPAD females, P-value=0.216 for combined females, P-value=0.299 for BPAD males, P-value=0.099 for combined males		Negative

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

Gene	Statistical Values/Author Comments	Result Category
DISC1	Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetio...... Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD. More...	Positive
TSNAX	Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetio...... Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD. More...	Positive

Gene-gene interactions reported by this study for BD (count: 1)

Gene Group	Markers	Statistical Values	Author Comments	Result Category
TSNAX DISC1	rs766288 - rs3738401 - rs2812393 - rs821616; rs766288 - rs821616; rs766288 - rs2812393	P-value < 0.05 for markers "rs766288-rs3738401-rs2812393-rs821616" with haplotype "C-G-G-T" and "A-G-G-T", "rs766288-rs821616" with haplotype "C-A", "A-A" and "A-T", "rs766288-rs2812393" with haplotype "C-C" and "A-G" for BPAD or BPAD&SZ.	Several markers among thest two genes were tested associated...... Several markers among thest two genes were tested associated with BPAD or BPAD&SZ. More...	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	rs2812393	DISC1 TSNAX	SZ patients: P-value=0.093, P-value=0.026 for females, P-value=0.775 for males; BPAD&SCZ: P-value=0.073, P-value=0.028 for females, P-value=0.668 for males	Moderate associations were also observed in females for rs2812393 (SCZ, P=0.026; BPAD&SCZ, P=0.028).	Positive
SZ	rs3738401	DISC1 TSNAX	SZ patients: P-value=0.794, P-value=0.473 for females, P-value=0.427 for males; BPAD&SCZ: P-value=0.520, P-value=0.875 for females, P-value=0.529 for males		Negative
SZ	rs766288	TSNAX DISC1	SZ patients: P-value=0.906, P-value=0.03 for females, P-value=0.105 for males; BPAD&SCZ: P-value=0.336, P-value=0.004 for females, P-value=0.248 for males	The most significant association was found for combined female cases of BPAD or SCZ. Moderate associations were also observed in females for rs766288 (SCZ, P=0.03)	Positive
SZ	rs821616	DISC1 TSNAX	SZ patients: P-value=0.179, P-value=0.213 for females, P-value=0.579 for males; BPAD&SCZ: P-value=0.04, P-value=0.138 for females, P-value=0.183 for males	One SNP (rs821616) showed moderate significant association with cases compared with controls in regression analysis	Positive

Haplotypes reported by this study for SZ/MDD

Disease	Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Description	Result Category
SZ	rs2812393 - rs821616	G-A	DISC1	P-value=0.976 for SCZ, P-value=0.806 for combined cases, P-value=0.958 for SCZ females, P-value=0.834 for combined females, P-value=0.941 for SCZ males, P-value=0.898 for combined males		Negative
SZ	rs2812393 - rs821616	G-T	DISC1	P-value=0 for SCZ, P-value=0.001 for combined cases, P-value=0.007 for SCZ females, P-value=0.005 for combined females, P-value=0.02 for SCZ males, P-value=0.039 for combined males	Allelic combinations of G-T in SCZ (P=0), combined cases of BPAD or SCZ (P=0.001), SCZ females (P=0.007) and combined females (P=0.005) were observed to be protective combination of alleles. These combinations survived multiple corrections. In addition allelic combinations of G-T showed nominal significance, but did not withstand FDR corrections.	Positive
SZ	rs766288 - rs2812393	A-C	TSNAX DISC1	P-value=0.529 for SCZ, P-value=0.632 for combined cases, P-value=0.626 for SCZ females, P-value=0.216 for combined females, P-value=0.175 for SCZ males, P-value=0.099 for combined males		Negative
SZ	rs2812393 - rs821616	C-A	DISC1	P-value=0.236 for SCZ, P-value=0.125 for combined cases, P-value=0.078 for SCZ females, P-value=0.077 for combined females, P-value=0.931 for SCZ males, P-value=0.673 for combined males		Negative
SZ	rs2812393 - rs821616	C-T	DISC1	P-value=0.381 for SCZ, P-value=0.531 for combined cases, P-value=0.659 for SCZ females, P-value=0.642 for combined females, P-value=0.119 for SCZ males, P-value=0.206 for combined males		Negative
SZ	rs766288 - rs821616	C-T	TSNAX DISC1	P-value=0.093 for SCZ, P-value=0.115 for combined cases, P-value=0.307 for SCZ females, P-value=0.489 for combined females, P-value=0.177 for SCZ males, P-value=0.138 for combined males		Negative
SZ	rs766288 - rs821616	A-A	TSNAX DISC1	P-value=0.42 for SCZ, P-value=0.831 for combined cases, P-value=0.074 for SCZ females, P-value=0.022 for combined females, P-value=0.016 for SCZ males, P-value=0.028 for combined males	Few additional combinations that were found to be significantly associated after multiple corrections (n=12) were A-T in BPAD females (P=0.012, protective combination); C-A (P=0.014, risk combination), C-A in SCZ females (P=0.011, risk combination), A-T in combined female cases (P=0.012, protective combination) and A-A in combined female cases (P=0.022, protective combination) compared with control females. However nominal significance observed in BPAD (C-A, P=0.024, risk combination), cases with the combined phenotype (C-A, P=0.019, risk combination), SCZ males (A-A, P=0.016, risk combination) and males with the combined phenotype (A-A, P=0.028, risk combination), which did not withstand the multiple corrections.	Positive
SZ	rs766288 - rs821616	C-A	TSNAX DISC1	P-value=0.082 for SCZ, P-value=0.019 for combined cases, P-value=0.011 for SCZ females, P-value=0.004 for combined females, P-value=0.901 for SCZ males, P-value=0.589 for combined males	Allelic combination C-A (P=0.004) in the female cases with combined phenotype showed significant association when multiple corrections were performed for all tests within each stratified gender (combined, females, males).	Positive
SZ	rs766288 - rs3738401 - rs2812393 - rs821616	A-G-G-T	TSNAX DISC1	P-value=0.0469 for BPAD&SZ, P-value=0.0209 for BPAD females &SCZ females	Haplotype A-G-G-T was also underrepresented in combined cases of BPAD or SCZ (P=0.0469), BPAD females (P=0.0273) and pooled females of BPAD or SCZ (P=0.0209).	Positive
SZ	rs766288 - rs2812393	C-G	TSNAX DISC1	P-value=0.46 for SCZ, P-value=0.703 for combined cases, P-value=0.626 for SCZ females, P-value=0.969 for combined females, P-value=0.639 for SCZ males, P-value=0.672 for combined males		Negative
SZ	rs766288 - rs2812393	A-G	TSNAX DISC1	P-value=0.62 for SCZ, P-value=0.551 for combined cases, P-value=0.016 for SCZ females, P-value=0.013 for combined females, P-value=0.174 for SCZ males, P-value=0.212 for combined males	Other combinations in BPAD females (C-C, P=0.003, risk combination) and SCZ females (C-C, P=0.011, risk combination; A-G, P=0.016, protective combination), combined female cases (A-G, P=0.013, protective combination; C-C, P=0.001, risk combination) were found to be significantly associated after FDR corrections.	Positive
SZ	rs766288 - rs2812393	C-C	TSNAX DISC1	P-value=0.099 for SCZ, P-value=0.016 for combined cases, P-value=0.011 for SCZ females, P-value=0.001 for combined females, P-value=0.993 for SCZ males, P-value=0.703 for combined males	Analyses of these two SNPs showed significant associations with allelic combination C-C (P=0.009) in the BPAD phenotype when multiple corrections were performed for all tests within each stratified gender (combined, females, males).	Positive
SZ	rs766288 - rs821616	A-T	TSNAX DISC1	P-value=0.577 for SCZ, P-value=0.215 for combined cases, P-value=0.097 for SCZ females, P-value=0.012 for combined females, P-value=0.476 for SCZ males, P-value=0.606 for combined males	Few additional combinations that were found to be significantly associated after multiple corrections (n=12) were A-T in BPAD females (P=0.012, protective combination); C-A (P=0.014, risk combination), C-A in SCZ females (P=0.011, risk combination), A-T in combined female cases (P=0.012, protective combination) and A-A in combined female cases (P=0.022, protective combination) compared with control females. However nominal significance observed in BPAD (C-A, P=0.024, risk combination), cases with the combined phenotype (C-A, P=0.019, risk combination), SCZ males (A-A, P=0.016, risk combination) and males with the combined phenotype (A-A, P=0.028, risk combination), which did not withstand the multiple corrections.	Positive
SZ	rs766288 - rs3738401 - rs2812393 - rs821616	C-G-G-T	TSNAX DISC1	P-value=0.0189 for SCZ, P-value=0.0065 for BPAD&SCZ, P-value=0.0205 for BPAD males & SCZ males	C-G-G-T haplotype showed relatively lesser frequency in BPAD (P=0.028), SCZ (P=0.0189) and combined cases of BPAD or SCZ (P=0.0065) and combined males of BPAD or SCZ (P=0.0205) compared with controls.	Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	DISC1	Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD.	Positive
SZ	TSNAX	Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD.	Positive

Gene-gene interactions reported by this study for SZ/MDD

Disease	Gene Group	Markers	Statistical Values	Description	Result Category
SZ		rs766288 - rs3738401 - rs2812393 - rs821616; rs766288 - rs821616; rs766288 - rs2812393	P-value < 0.05 for markers "rs766288-rs3738401-rs2812393-rs821616" with haplotype "C-G-G-T" and "A-G-G-T", "rs766288-rs821616" with haplotype "C-A", "A-A" and "A-T", "rs766288-rs2812393" with haplotype "C-C" and "A-G" for SCZ or BPAD&SCZ.	Several markers among thest two genes were tested associated with SCZ or BPAD&SCZ.	Positive