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	Smith, E. N.,2009 PMID: 19488044
Citation	Smith, E. N., C. S. Bloss, et al. (2009). Genome-wide association study of bipolar disorder in European American and African American individuals. Mol Psychiatry 14(8): 755-763.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	1346 BD cases (1001 EA subjects and 345 AA subjects) and 1703 control(1033 EA subjects and 670 AA subjects)
SNP/Region/Marker Size	702,044 SNPs
Predominant Ethnicity
Population	European American and African American

Detail Info

Technique	genotyping
Statistical Method	All genetic analyses were conducted using PLINK versions 1.03 and 1.04.(1) single locus, contingency table analysis with genomic control adjustment, (2)logistic regression using Local Ancestry in Admixed Populations (LAMP19)-derived estimates of ancestry as a covariate and (3) logistic regression using the top four multidimensional scaling (MDS) dimensions as covariates. LAMP ancestry estimateswere also compared to STRUCTURE20 estimates and were similar.Haplotype analyses were performed in the EA population using the sliding window approach in PLINK.
Result Summary	For the EA sample, single-nucleotide polymorphisms (SNPs) with the strongest statistical evidence for association included rs5907577 in an intergenic region at Xq27.1 (P=1.6 x 10(-6)) and rs10193871 in NAP5 at 2q21.2 (P=9.8 x 10(-6)). For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P=1.5 x 10(-6)) and rs2769605 in NTRK2 at 9q21.33 (P=4.5 x 10(-5)). We also investigated whether we could provide support for three regions previously associated with BD, and we showed that the ANK3 region replicates in our sample, along with some support for C15Orf53; other evidence implicates BD candidate genes such as SLITRK2. We also tested the hypothesis that BD susceptibility variants exhibit genetic background-dependent effects. SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P=1.4 x 10(-6)), rs4657247 in RGS5 at 1q23.3 (P=4.1 x 10(-6)), and rs7078071 in BTBD16 at 10q26.13 (P=4.5 x 10(-6)). This study is the first to conduct GWA of BD in individuals of AA and suggests that genetic variations that contribute to BD may vary as a function of ancestry.

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs6046396	RIN2		G	EA Pritzker non-overlap: Alelle association: MAF=0.29, Multidimensional scaling: OR=1.54, P-value = 0.00000143; LAMP adjusted: OR=1.56, P-value = 0.00000062; Genomic control: OR=1.57, P-value = 0.000000493		Trend
rs5907577	RN7SL727P		T	EA only: Alelle association: MAF=0.31, Multidimensional scaling: OR=1.48, P-value = 0.0000016; LAMP adjusted: OR=1.47, P-value = 0.0000021; Genomic control: OR=1.444, P-value = 0.0000046		Trend
rs7078071	BTBD16		T	EA/AA combined sample: MAF=0.1, OR=2.85, SNP ancestry interaction P-value = 0.0000045		Trend
rs2769605	NTRK2		T	AA only: Alelle association: MAF=0.22, Multidimensional scaling: OR=0.6, P-value = 0.000045; LAMP adjusted: OR=0.61, P-value = 0.000045; Genomic control: OR=0.63, P-value = 0.00015		Trend
rs1825828			C	EA only: Alelle association: MAF=0.26, Multidimensional scaling: OR=0.7, P-value = 0.0000007; LAMP adjusted: OR=0.7, P-value = 0.00000076; Genomic control: OR=0.68, P-value = 0.00000029		Trend
rs2111504	DPY19L3		T	AA only: Alelle association: MAF=0.23, Multidimensional scaling: OR=1.74, P-value = 0.0000015; LAMP adjusted: OR=1.73, P-value = 0.0000017; Genomic control: OR=1.66, P-value = 0.000005		Trend
rs11208285	RORA		A	EA/AA combined sample: MAF=0.38, OR=2.05, SNP ancestry interaction P-value = 0.0000014		Trend
rs4825220			C	EA/AA combined: Alelle association: MAF=0.37, Multidimensional scaling: OR=0.71, P-value = 0.00000026; LAMP adjusted: OR=0.7, P-value = 0.00000019; Genomic control: OR=0.61, P-value = 0.8496		Trend
rs10193871	NCKAP5		G	EA only: Alelle association: MAF=0.13, Multidimensional scaling: OR=0.65, P-value = 0.0000098; LAMP adjusted: OR=0.65, P-value = 0.0000071; Genomic control: OR=0.65, P-value = 0.0000088		Trend
rs4657247	RGS5		T	EA/AA combined sample: MAF=0.21, OR=2.11, SNP ancestry interaction P-value = 0.0000041		Trend

Genes reported by this study for BD (count: 7)

Gene	Statistical Values/Author Comments	Result Category
BTBD16	SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in R...... SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P=1.4E-06), rs4657247 in RGS5 at 1q23.3 (P=4.1E-06), and rs7078071 in BTBD16 at 10q26.13 (P=4.5E-06). More...	Trend
RGS5	SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in R...... SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P=1.4E-06), rs4657247 in RGS5 at 1q23.3 (P=4.1E-06), and rs7078071 in BTBD16 at 10q26.13 (P=4.5E-06). More...	Trend
RIN2	Suggestive association of this gene was found. Suggestive association of this gene was found.	Trend
NTRK2	For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 i...... For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P=1.5E-06) and rs2769605 in NTRK2 at 9q21.33 (P=4.5E-05). More...	Trend
DPY19L3	For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 i...... For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P=1.5E-06) and rs2769605 in NTRK2 at 9q21.33 (P=4.5E-05). More...	Trend
ROR1	SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in R...... SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P=1.4E-06), rs4657247 in RGS5 at 1q23.3 (P=4.1E-06), and rs7078071 in BTBD16 at 10q26.13 (P=4.5E-06). More...	Trend
NCKAP5	For the EA sample, single-nucleotide polymorphisms (SNPs) with the strongest statistical evidence fo...... For the EA sample, single-nucleotide polymorphisms (SNPs) with the strongest statistical evidence for association included rs5907577 in an intergenic region at Xq27.1 (P=1.6E-06) and rs10193871 in NAP5 at 2q21.2 (P=9.8E-06). More...	Trend