Meta-analysis Report

Basic Info

Reference	McMahon, F. J., 2010 PMID: 20081856
Citation	McMahon, F. J., N. Akula, et al. (2010). "Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1." Nat Genet 42(2): 128-131.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Type	Candidate-gene association study

Detail Info

Samples	Over 13,600 individuals genotyped on high-density SNP arrays from five case-control cohorts were analyzed.All individuals were of European ancestry.
Statistic Method	Genotype data from the NIMH-BP, GAIN-MDD and German samples were used to impute data on 2.1 million HapMap Phase 2 SNPs by use of the program Markov Chain Haplotyping (MACH), version 1.0 (ref. 20). Selected results were confirmed, and heterogeneity statistics were calculated, using Comprehensive Meta-analysis, version 2.0. We used a threshold of genome-wide significance (7.2E-8) derived from a published, genome-wide simulation of common variants in samples of European ancestry. Power analysis was done with Genetic Power Calculator.
Basic Result	We identified SNPs at 3p21.1 associated with major mood disorders (rs2251219, P = 3.63E-8; odds ratio = 0.87; 95% confidence interval, 0.83-0.92), with supportive evidence for association observed in two out of three independent replication cohorts. These results provide an example of a shared genetic susceptibility locus for bipolar disorder and MDD.

Genetic factors reported by this study for BD

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

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs2251219	PBRM1 SMIM4 RNU6-856P			P-value = 3.63E-8, odds ratio = 0.87, 95% confidence interval=0.83-0.92 for all major mood disorders. The C allele was consistently less common in cases than controls (P-value = 1.12E-8).	rs2251219 was significantly associated with major mood disor...... rs2251219 was significantly associated with major mood disorder. The findings were more robust in bipolar disorder than in MDD.The result is replicable in replication samples. We did not find a significant association signal at any of these loci after genome-wide correction for multiple testing. Our genetic association results provide support for the previous epidemiologic evidence of genetic overlap between bipolar disorder and MDD. More...	Positive
rs2289247	GLT8D1 GNL3 SNORD19 SNORD69 SNORD19B				There was strong linkage disequilibrium (LD) between rs22512...... There was strong linkage disequilibrium (LD) between rs2251219 and rs2289247, which is significant in the GAIN-MDD sample. More...	Positive

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

Gene	Statistical Values/Author Comments	Result Category
GNL3	A nonsynonymous variant rs2289247 in the gene GNL3 was significant in MDD and there was strong linka...... A nonsynonymous variant rs2289247 in the gene GNL3 was significant in MDD and there was strong linkage disequilibrium (LD) between rs2251219 and rs2289247. More...	Positive
PBRM1	A synonymous variant rs2251219 in the gene PBRM1 was significant in major mood disorders. A synonymous variant rs2251219 in the gene PBRM1 was significant in major mood disorders.	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
MDD	rs2251219	PBRM1 SMIM4 RNU6-856P		rs2251219 was significantly associated with major mood disorder. The findings were more robust in bipolar disorder than in MDD.The result is replicable in replication samples. We did not find a significant association signal at any of these loci after genome-wide correction for multiple testing. Our genetic association results provide support for the previous epidemiologic evidence of genetic overlap between bipolar disorder and MDD.	Positive
MDD	rs2289247	GLT8D1 GNL3 SNORD19 SNORD69 SNORD19B	P-value = 8.96E-7 for a meta-analysis in the GAIN-MDD sample.	It is significant in the GAIN-MDD sample.	Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
MDD	PBRM1	A synonymous variant in the gene PBRM1 was significant in major mood disorders.	Positive
MDD	GNL3	A nonsynonymous variant in the gene GNL3 was significant in MDD.	Positive