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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Study Report

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Basic Info

Reference	Feng, Y., 2008 PMID: 18347002
Citation	Feng, Y., A. Vetro, et al. (2008). "Association of the neurotrophic tyrosine kinase receptor 3 (NTRK3) gene and childhood-onset mood disorders." Am J Psychiatry 165(5): 610-616.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	The analyses for this study were based on the genotypes of 603 families with 723 affected children.
SNP/Region/Marker Size	18 SNPs
Predominant Ethnicity	Caucasian
Population	Hungarian
Age Group	Children : The probands met DSM-IV criteria for a mood disorder (depressive disorder or bipolar disorder), with the onset of the first episode by 14.9 years of age. For 14 of the siblings, onset of depression occurred between ages 15 and 18.

Detail Info

Sample Diagnosis	DSM-IV and the Interview Schedule for Children and Adolescents-Diagnostic Version
Sample Status	At the time of diagnosis, 0.8% of the children met the criteria for bipolar disorder. Given the young age of the children, we expect that 20% to 30% of those who are currently diagnosed with unipolar depression will develop bipolar disorder as they mature.
Technique	genotyping, DNA was extracted from blood using a standard high salt method.
Statistical Method	All data were screened for Mendelian errors using PEDSTATS, and MERLIN was used to detect any crossovers between markers. We used the extended transmission disequilibrium test program for analyses of the transmission disequilibrium test of single markers. One thousand permutation tests were conducted using the UNPHASED program to correct p values for multiple testing. This analysis produces a significance level that corrects for the number of markers analyzed while taking into account the correlation between markers. One thousand permutations were run using the 'robust permutation' option, which is robust to prior linkage. Association of haplotypes was evaluated using TRANSMIT with the 'robust estimator' option. Haplotypes with frequencies less than 10% were pooled, and X² and p values are reported only for those with frequencies greater than 10%. The degree of linkage disequilibrium (LD) between markers was evaluated using Haploview 3.2
Result Summary	Results identified significant evidence for association for five of the markers across the NTRK3 gene using the transmission disequilibrium test. Four of the five markers were located in a region of strong linkage disequilibrium and were highly correlated. Haplotype results provided significant evidence for association to haplotypes composed of markers located in two haplotype blocks.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs3825885	NTRK3		C	TDT P-value = 0.181, X²(df=1)=1.791		Negative
rs7174354	NTRK3		G	TDT P-value = 0.208, X²(df=1)=1.588		Negative
rs922231	NTRK3		T	TDT P-value = 0.47, X²(df=1)=0.521		Negative
rs991729	NTRK3		A	TDT P-value = 0.18, X²(df=1)=1.801		Negative
rs3825884	NTRK3		A	TDT P-value = 0.086, X²(df=1)=2.945		Negative
rs3784441	NTRK3		A	TDT P-value = 0.156, X²(df=1)=2.01		Negative
rs3784410	NTRK3		T	TDT P-value = 0.058, X²(df=1)=3.6		Negative
rs3784406	NTRK3 MED28P6		A	TDT P-value = 0.025, X²(df=1)=5.013		Positive
rs2059588	NTRK3		C	TDT P-value = 0.018, X²(df=1)=5.633	The most significant marker, with a p value of 0.018. This v...... The most significant marker, with a p value of 0.018. This value did not maintain global significance after permutation testing (p=0.2178, SE=0.01305). More...	Positive
rs1948066	NTRK3		T	TDT P-value = 0.701, X²(df=1)=0.147		Negative
rs1834573	NTRK3		T	TDT P-value = 0.428, X²(df=1)=0.627		Negative
rs1559824	NTRK3		A	TDT P-value = 0.774, X²(df=1)=0.082		Negative
rs1529323	NTRK3		A	TDT P-value = 0.076, X²(df=1)=3.149		Negative
rs1435403	NTRK3		A	TDT P-value = 0.12, X²(df=1)=2.421		Negative
rs1369430	NTRK3		G	TDT P-value = 0.025, X²(df=1)=5.055		Positive
rs1369423	NTRK3		A	TDT P-value = 0.925, X²(df=1)=0.009		Negative
rs1110306	NTRK3		A	TDT P-value = 0.035, X²(df=1)=4.445		Positive
rs11073767	NTRK3		T	TDT P-value = 0.036, X²(df=1)=4.408		Positive

Haplotypes reported by this study for BD (count: 10)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs2059588 - rs1110306 - rs3784406	TGT	NTRK3	haplotype TGT P-value = 0.037, X<sup>2</sup>(df=1)=4.335	haplotype with frequency greater than 10% was biased in tran...... haplotype with frequency greater than 10% was biased in transmission More...	Positive
rs2059588 - rs1110306 - rs3784406		NTRK3	Global X<sup>2</sup>=12.924, df=7, p=0.074. For haplotypes with frequencies greater than 10%, X<sup>2</sup>=6.617, df=2, p=0.037.		Positive
rs1369430 - rs1435403 - rs3784441	GAA	NTRK3	haplotype GAA P-value = 0.095, X<sup>2</sup>(df=1)=2.789		Negative
rs1369430 - rs1435403 - rs3784441	AGG	NTRK3	haplotype AGG P-value = 0.002, X<sup>2</sup>(df=1)=9.704	the common haplotype (frequency 0.62) was overtransmitted to...... the common haplotype (frequency 0.62) was overtransmitted to affected offspring More...	Positive
rs991729 - rs3784410	GC	NTRK3	haplotype GC P-value = 0.141, X<sup>2</sup>(df=1)=2.170		Negative
rs991729 - rs3784410	GT	NTRK3	haplotype GT P-value = 0.038, X<sup>2</sup>(df=1)=4.310		Positive
rs991729 - rs3784410		NTRK3	Global X<sup>2</sup>=5.442, df=3, p=0.142. For haplotypes with frequencies greater than 10%, X<sup>2</sup>=5.442, df=3, p=0.142.		Negative
rs2059588 - rs1110306 - rs3784406	CAG	NTRK3	haplotype CAG P-value = 0.011, X<sup>2</sup>(df=1)=6.440	haplotype with frequency greater than 10% was biased in tran...... haplotype with frequency greater than 10% was biased in transmission More...	Positive
rs991729 - rs3784410	AC	NTRK3	haplotype AC P-value = 0.436, X<sup>2</sup>(df=1)=0.608		Negative
rs1369430 - rs1435403 - rs3784441		NTRK3	Global X<sup>2</sup>=17.588, df=7, p=0.014. For haplotypes with frequencies greater than 10%, X<sup>2</sup>=11.262, df=2, p=0.004.		Positive

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