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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Basic Info

Reference	Palo, O. M., 2007 PMID: 17673452
Citation	Palo, O. M., M. Antila, et al. (2007). "Association of distinct allelic haplotypes of DISC1 with psychotic and bipolar spectrum disorders and with underlying cognitive impairments." Hum Mol Genet 16(20): 2517-2528.
Disease Type	Bipolar Disorder
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	723 individuals from 175 nuclear families and from four extended families and 57 trios as a control sample in the molecular genetic analyses
SNP/Region/Marker Size	13 SNPs
Predominant Ethnicity	Caucasian
Population	Finnish
Gender	118 males and 109 females in the group of patients with Bipolar spectrum disorder, 101 males and 70 females in the control group

Detail Info

Sample Diagnosis	Structural Clinical Interview for DSM-IV Axis I Disorders (SCID)
Sample Status	All individuals born between 1940 and 1969 and hospitalized with a diagnosis of BPD were identified from the Finnish National Hospital Discharge Register. The study sample comprised a group of patients with bipolar spectrum disorders, i.e. BPD type I and II, NOS and cyclothymia, including BPD type I (n=214), II (n=5), NOS (n= 6) and cyclothymia (n=2), and a group of patients with psychotic disorders, i.e. BPD type I with intermittent psychotic features, psychotic depression, SCZ, SA disorder and psychosis NOS (n=251), with an overlap of 162 individuals belonging to both groups.
Technique	genotyping using the homogenous Mass Extension reaction on the Sequenom MassARRAY System
Statistical Method	Single-marker association analysis was conducted using the Pseudomarker program; Haplotype analysis was performed using the TRANSMIT 2.5.4. program.
Result Summary	Consistent with an earlier finding in Finnish SCZ families, the haplotype T-A of rs751229 and rs3738401 at the 5' end of DISC1 was over-transmitted to males with psychotic disorder (P=0.008; for an extended haplotype P=0.0007 with both genders). Haplotypes at the 3' end of DISC1 associated with bipolar spectrum disorder (P=0.0002 for an under-transmitted haplotype T-T of rs821616 and rs1411771, for an extended haplotype P=0.0001), as did a two-SNP risk haplotype at the 5' end of TSNAX (P=0.007). The risk haplotype for psychotic disorder also associated to perseverations (P=0.035; for rs751229 alone P=0.0012), and a protective haplotype G-T-G with rs1655285 in addition to auditory attention (P=0.0059). The 3' end variants associated with several cognitive traits, with the most robust signal for rs821616 and verbal fluency and rs980989 and psychomotor processing speed (P=0.011 for both). These results support involvement of DISC1 in the genetic aetiology of BPD and suggest that its distinct variants contribute to variation in the dimensional features of psychotic and bipolar spectrum disorders.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs1655285	TSNAX	G/C		P-value = 0.025 in all patients, P-value = 0.708 in males, P-value = 0.088 in females, with bipolar spectrum disorder	observed weak evidence for association of rs1655285 at intro...... observed weak evidence for association of rs1655285 at intron 5 of TSNAX with bipolar spectrum disorder More...	Positive
rs3738401	DISC1 TSNAX	G/A		P-value = 0.888 in all patients, P-value = 0.281 in males, P-value = 0.862 in females, with bipolar spectrum disorder	With psychotic disorder as an outcome, the analysis of indiv...... With psychotic disorder as an outcome, the analysis of individual SNPs in the complete sample provided only evidence of a trend for an association with rs3738401 in exon 2 (P=0.051, Pseudomarker). More...	Negative
rs6675281	DISC1 TSNAX	C/T		P-value = 0.48 in all patients, P-value = 0.522 in males, P-value = 0.292 in females, with bipolar spectrum disorder		Negative
rs751229	DISC1 TSNAX	T/C		P-value = 0.777 in all patients, P-value = 0.718 in males, P-value = 0.61 in females, with bipolar spectrum disorder		Negative
rs821616	DISC1 TSNAX	A/T		P-value = 0.218 in all patients, P-value = 0.256 in males, P-value = 0.221 in females, with bipolar spectrum disorder		Negative
rs967244	DISC1	A/G		P-value = 0.204 in all patients, P-value = 0.764 in males, P-value = 0.26 in females, with bipolar spectrum disorder		Negative
rs980989	DISC1	G/T		P-value = 0.708 in all patients, P-value = 0.315 in males, P-value = 0.791 in females, with bipolar spectrum disorder		Negative
rs1322784	DISC1 TSNAX	A/G		P-value = 0.139 in all patients, P-value = 0.92 in males, P-value = 0.332 in females, with bipolar spectrum disorder		Negative
rs1000731	DISC1 TSNAX	C/T		P-value = 0.475 in all patients, P-value = 0.16 in males, P-value = 0.115 in females, with bipolar spectrum disorder		Negative
rs1538977	DISC1 TSNAX	A/G		P-value = 0.718 in all patients, P-value = 0.058 in males, P-value = 0.862 in females, with bipolar spectrum disorder		Negative
rs1411771	DISC1 TSNAX	T/C		P-value = 0.406 in all patients, P-value = 0.296 in males, P-value = 1 in females, with bipolar spectrum disorder		Negative
rs1630250	TSNAX DISC1	G/C		P-value = 0.632 in all patients, P-value = 0.572 in males, P-value = 0.104 in females, with bipolar spectrum disorder		Negative
rs1615409	TSNAX DISC1	C/A		P-value = 0.74 in all patients, P-value = 1 in males, P-value = 0.233 in females, with bipolar spectrum disorder		Negative

Haplotypes reported by this study for BD (count: 18)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs1322784 - rs967244	A-G	DISC1	Individual P-value = 0.517 in all, P-value = 0.966 in males, P-value = 0.243 in females; global P-value = 0.849 in all, P-value = 0.819 in males, P-value = 0.338 in females, with bipolar spectrum disorder		Negative
rs1000731 - rs821616 - rs1411771	C-T-T	DISC1	Individual P-value = 0.009 in all, P-value = 0.045 in males, P-value = 0.135 in females; global P-value = 0.051 in all, P-value = 0.345 in males, P-value = 0.295 in females, with bipolar spectrum disorder		Positive
rs1000731 - rs821616	C-T	DISC1	Individual P-value = 0.043 in all, P-value = 0.157 in males, P-value = 0.237 in females; global P-value = 0.025 in all, P-value = 0.208 in males, P-value = 0.218 in females, with bipolar spectrum disorder		Positive
rs6675281 - rs1000731	T-C	DISC1	Individual P-value = 0.417 in all, P-value = 0.569 in males, P-value = 0.662 in females; global P-value = 0.274 in all, P-value = 0.727 in males, P-value = 0.321 in females, with bipolar spectrum disorder		Negative
rs3738401 - rs1538977	A-A	DISC1	Individual P-value = 0.17 in all, P-value = 0.347 in males, P-value = 0.324 in females; global P-value = 0.426 in all, P-value = 0.254 in males, P-value = 0.749 in females, with bipolar spectrum disorder		Negative
rs1538977 - rs1322784	A-A	DISC1	Individual P-value = 0.622 in all, P-value = 0.952 in males, P-value = 0.363 in females; global P-value = 0.683 in all, P-value = 0.689 in males, P-value = 0.757 in females, with bipolar spectrum disorder		Negative
rs1411771 - rs980989	T-G	DISC1	Individual P-value = 0.269 in all, P-value = 0.85 in males, P-value = 0.185 in females; global P-value = 0.429 in all, P-value = 0.631 in males, P-value = 0.43 in females, with bipolar spectrum disorder		Negative
rs1655285 - rs751229 - rs3738401	G-T-A	TSNAX DISC1	Individual P-value = 0.261 in all, P-value = 0.039 in males, P-value = 0.965 in females; global P-value = 0.42 in all, P-value = 0.183 in males, P-value = 0.426 in females, with bipolar spectrum disorder		Positive
rs1615409 - rs1655285 - rs751229	C-G-T	TSNAX DISC1	Individual P-value = 0.085 in all, P-value = 0.234 in males, P-value = 0.204 in females; global P-value = 0.114 in all, P-value = 0.287 in males, P-value = 0.106 in females, with bipolar spectrum disorder		Negative
rs1655285 - rs751229	G-T	TSNAX DISC1	Individual P-value = 0.399 in all, P-value = 0.704 in males, P-value = 0.418 in females; global P-value = 0.188 in all, P-value = 0.427 in males, P-value = 0.047 in females, with bipolar spectrum disorder		Positive
rs821616 - rs1411771	T-T	DISC1	Individual P-value = 0.0002 in all, P-value = 0.011 in males, P-value = 0.016 in females; global P-value = 0.004 in all, P-value = 0.07 in males, P-value = 0.092 in females, with bipolar spectrum disorder	the haplotype at the 3' end of DISC1, composed of SNPs rs821...... the haplotype at the 3' end of DISC1, composed of SNPs rs821616 and rs1411771, was under-transmitted to affected females and males More...	Positive
rs821616 - rs1411771 - rs980989	T-T-G	DISC1	Individual P-value = 0.0001 in all, P-value = 0.005 in males, P-value = 0.021 in females; global P-value = 0.021 in all, P-value = 0.115 in males, P-value = 0.214 in females, with bipolar spectrum disorder	An extended allelic haplotype including rs821616, rs1411771 ...... An extended allelic haplotype including rs821616, rs1411771 and in addition rs980898, was also under-transmitted to affected males and females More...	Positive
rs6675281 - rs1000731 - rs821616	T-C-T	DISC1	Individual P-value = 0.022 in all, P-value = 0.105 in males, P-value = 0.59 in females; global P-value = 0.033 in all, P-value = 0.201 in males, P-value = 0.486 in females, with bipolar spectrum disorder		Positive
rs751229 - rs3738401	T-A	DISC1	Individual P-value = 0.159 in all, P-value = 0.146 in males, P-value = 0.682 in females; global P-value = 0.274 in all, P-value = 0.563 in males, P-value = 0.404 in females, with bipolar spectrum disorder		Negative
rs1630250 - rs1615409	G-C	TSNAX	Individual P-value = 0.007 in all, P-value = 0.052 in males, P-value = 0.098 in females; global P-value = 0.007 in all, P-value = 0.052 in males, P-value = 0.097 in females, with bipolar spectrum disorder	a major haplotype containing rs1630250 and rs1615409 within ...... a major haplotype containing rs1630250 and rs1615409 within the TSNAX gene was over-transmitted to affected females and males More...	Positive
rs1630250 - rs1615409 - rs1655285	G-C-G	TSNAX	Individual P-value = 0.065 in all, P-value = 0.153 in males, P-value = 0.286 in females; global P-value = 0.089 in all, P-value = 0.11 in males, P-value = 0.378 in females, with bipolar spectrum disorder		Negative
rs967244 - rs6675281	G-T	DISC1	Individual P-value = 0.278 in all, P-value = 0.329 in males, P-value = 0.462 in females; global P-value = 0.576 in all, P-value = 0.449 in males, P-value = 0.673 in females, with bipolar spectrum disorder		Negative
rs1615409 - rs1655285	C-G	TSNAX	Individual P-value = 0.078 in all, P-value = 0.201 in males, P-value = 0.248 in females; global P-value = 0.102 in all, P-value = 0.162 in males, P-value = 0.361 in females, with bipolar spectrum disorder		Negative

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

Gene	Statistical Values/Author Comments	Result Category
DISC1	The results provide evidence for an association of distinct allelic variants of DISC1 to psychotic a...... The results provide evidence for an association of distinct allelic variants of DISC1 to psychotic and bipolar spectrum disorders. More...	Positive
TSNAX	The results provide evidence for an association of distinct allelic variants of TSNAX to psychotic a...... The results provide evidence for an association of distinct allelic variants of TSNAX to psychotic and bipolar spectrum disorders More...	Positive

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

Gene Group	Markers	Statistical Values	Author Comments	Result Category
TSNAX DISC1	rs1655285 - rs751229; rs1615409 - rs1655285 - rs751229; rs1655285 - rs751229 - rs3738401	Haplotype cross these two genes were tested. For haplotype "rs1655285-rs751229(G-T)": Individual P-value = 0.399 in all, P-value = 0.704 in males, P-value = 0.418 in females; global P-value = 0.188 in all, P-value = 0.427 in males, P-value = 0.047 in females, with bipolar spectrum disorder; For haplotype "rs1615409 - rs1655285 - rs751229(C-G-T)": Individual P-value = 0.085 in all, P-value = 0.234 in males, P-value = 0.204 in females; global P-value = 0.114 in all, P-value = 0.287 in males, P-value = 0.106 in females, with bipolar spectrum disorder; For haplotype "rs1655285 - rs751229 - rs3738401(G-T-A)": Individual P-value = 0.261 in all, P-value = 0.039 in males, P-value = 0.965 in females; global P-value = 0.42 in all, P-value = 0.183 in males, P-value = 0.426 in females, with bipolar spectrum disorder.	Significant association were found in rs1655285-rs751229 an...... Significant association were found in rs1655285-rs751229 and rs1655285-rs751229-rs3738401. More...	Positive