Study Report

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Basic Info

Reference	Moskvina, V.,2009 PMID: 19065143
Citation	Moskvina, V., N. Craddock, et al. (2009). Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. Mol Psychiatry 14(3): 252-260.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	1868 bipolar disorder cases,479 UK schizophrenia cases and 2938 controls
SNP/Region/Marker Size	145,344 SNPs
Predominant Ethnicity
Population	WTCCC collection and British

Detail Info

Sample Status	The Bipolar data set was reported by the Wellcome Trust Case Control Consortium (WTCCC) and consists of 1868 cases and 2938 controls typed with the GeneChip 500K Mapping Array Set. The UK schizophrenia cases (n = 479) were not part of that study but were typed contemporaneously with the WTCCC samples using the same pipeline.
Technique	genotyping
Statistical Method	the Armitage trend test (1df) ,The corrected P-values were then in turn used to generate three types of gene-wide tests. The first was based on the smallest SNP P-value per gene, and the second and third were, respectively, the threshold-truncated product of all SNP P-values within a gene where the truncation thresholds were P<=0.01 and P<=0.001.To calculate empirical gene-wide significance for each gene, we performed 1000 genome-wide permutations for each GWAS data set.
Result Summary	For each data set and at a range of statistical thresholds, we observed significantly more SNPs within genes (P(min) for excess<0.001) showing evidence for association than expected whereas this was not true for extragenic SNPs (P(min) for excess>0.1). At a range of thresholds of significance, we also observed substantially more associated genes than expected (P(min) for excess in schizophrenia=1.8 x 10(-8), in bipolar=2.4 x 10(-6)). Moreover, an excess of genes showed evidence for association across disorders. Among those genes surpassing thresholds highly enriched for true association, we observed evidence for association to genes reported in other GWAS data sets (CACNA1C) or to closely related family members of those genes including CSF2RB, CACNA1B and DGKI. Our analyses show that association signals are enriched in and around genes, large numbers of genes contribute to both disorders and gene-wide analyses offer useful complementary approaches to more standard methods.

Genetic factors reported by this study for BD

Genes reported by this study for BD (count: 52)

Gene	Statistical Values/Author Comments	Result Category
DFNB31	In BP:Smallest P-value per gene=0.0004, Product of P truncation <=0.01=0.00229, Product of P truncation <=0.001=0.0003. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
RNPEPL1	In BP:Smallest P-value per gene=0.00005, Product of P truncation <=0.01=0.00001, Product of P truncation <=0.001=0.00001. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
ITIH3	In BD:Smallest P-value per gene=0.0016, Product of P truncation <=0.01=0.0016, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
PBRM1	In BD:Smallest P-value per gene=0.00856, Product of P truncation <=0.01=0.00246, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
PALB2	In BP:Smallest P-value per gene=0.0005, Product of P truncation <=0.01=0.0005, Product of P truncation <=0.001=0.0005. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
JAM3	In BD:Smallest P-value per gene=0.00245, Product of P truncation <=0.01=0.00196, Product of P truncation <=0.001=0.00444. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
TP53I3	In BD:Smallest P-value per gene=0.0087, Product of P truncation <=0.01=0.0087, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
RSRC2	In BP:Smallest P-value per gene=0.00439, Product of P truncation <=0.01=0.00015, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
FABP3	In BP:Smallest P-value per gene=0.01657, Product of P truncation <=0.01=0.00075, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
INTS6	In BD:Smallest P-value per gene=0.01196, Product of P truncation <=0.01=0.00611, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
GLT8D1	In BD:Smallest P-value per gene=0.00535, Product of P truncation <=0.01=0.00535, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
C10orf120	In BD:Smallest P-value per gene=0.00705, Product of P truncation <=0.01=0.00709, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
MCM3AP-AS1	In BP:Smallest P-value per gene=0.00146, Product of P truncation <=0.01=0.00096, Product of P truncation <=0.001=0.00147. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
PFN4	In BD:Smallest P-value per gene=0.00744, Product of P truncation <=0.01=0.00744, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
SEMG2	In BD:Smallest P-value per gene=0.00849, Product of P truncation <=0.01=0.00849, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
SIGLEC6	In BP:Smallest P-value per gene=0.00069, Product of P truncation <=0.01=0.00211, Product of P truncation <=0.001=0.00087. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
AKAP10	In BP:Smallest P-value per gene=0.00024, Product of P truncation <=0.01=0.00016, Product of P truncation <=0.001=0.00022. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
CMTM8	In BP:Smallest P-value per gene=0.00024, Product of P truncation <=0.01=0.00007, Product of P truncation <=0.001=0.00027. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
CACNA1C	In BP:Smallest P-value per gene=0.03798, Product of P truncation <=0.01=0.0007, Product of P truncation <=0.001=0.00225. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
SVEP1	In BP:Smallest P-value per gene=0.00494, Product of P truncation <=0.01=0.00317, Product of P truncation <=0.001=0.00069. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
GNL3	In BD:Smallest P-value per gene=0.00792, Product of P truncation <=0.01=0.00797, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
ANKRD35	In BP:Smallest P-value per gene=0.00073, Product of P truncation <=0.01=0.00084, Product of P truncation <=0.001=0.00079. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
ZNF490	In BP:Smallest P-value per gene=0.00002, Product of P truncation <=0.01=0.00025, Product of P truncation <=0.001=0.00011. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
ZNF274	In BP:Smallest P-value per gene=0.00005, Product of P truncation <=0.01=0.00005, Product of P truncation <=0.001=0.00005. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
ZNF284	In BP:Smallest P-value per gene=0.00042, Product of P truncation <=0.01=0.00042, Product of P truncation <=0.001=0.00042. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
POLE2	In BP:Smallest P-value per gene=0.00939, Product of P truncation <=0.01=0.00094, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
CSF2RB	In BP:Smallest P-value per gene=0.00035, Product of P truncation <=0.01=0.0094, Product of P truncation <=0.001=0.00119. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
CPB2	In BP:Smallest P-value per gene=0.00034, Product of P truncation <=0.01=0.02652, Product of P truncation <=0.001=0.00309. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
NEK4	In BD:Smallest P-value per gene=0.00636, Product of P truncation <=0.01=0.00346, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
TDRD9	In BP:Smallest P-value per gene=<0.00001, Product of P truncation <=0.01=0.00521, Product of P truncation <=0.001=0.00092. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
CAPN10	In BP:Smallest P-value per gene=0.00078, Product of P truncation <=0.01=0.00138, Product of P truncation <=0.001=0.00093. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
LRR1	In BP:Smallest P-value per gene=0.00341, Product of P truncation <=0.01=0.0005, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
DPP10	In BP:Smallest P-value per gene=0.00032, Product of P truncation <=0.01=0.00019, Product of P truncation <=0.001=0.00011. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
LRRC36	In BP:Smallest P-value per gene=0.00037, Product of P truncation <=0.01=0.00037, Product of P truncation <=0.001=0.00037. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
TLE4	In BP:Smallest P-value per gene=0.00011, Product of P truncation <=0.01=0.02999, Product of P truncation <=0.001=0.00392. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
ATP6V0D1	In BP:Smallest P-value per gene=0.00061, Product of P truncation <=0.01=0.00067, Product of P truncation <=0.001=0.00061. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
PSKH1	In BD:Smallest P-value per gene=0.00169, Product of P truncation <=0.01=0.00169, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
WDFY2	In BD:Smallest P-value per gene=0.04086, Product of P truncation <=0.01=0.00399, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
TCAF1	In BP:Smallest P-value per gene=0.00095, Product of P truncation <=0.01=0.0016, Product of P truncation <=0.001=0.001. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
PTGR2	In BP:Smallest P-value per gene=0.00377, Product of P truncation <=0.01=0.00079, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
CDKN2A	In BD:Smallest P-value per gene=0.0063, Product of P truncation <=0.01=0.0063, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
TMEM108	In BD:Smallest P-value per gene=0.04004, Product of P truncation <=0.01=0.00735, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
KLHDC1	In BP:Smallest P-value per gene=0.00017, Product of P truncation <=0.01=0.00015, Product of P truncation <=0.001=0.00015. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
LAMP3	In BP:Smallest P-value per gene=0.00009, Product of P truncation <=0.01=0.00004, Product of P truncation <=0.001=0.00006. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
PTPRE	In BP:Smallest P-value per gene=0.00242, Product of P truncation <=0.01=0.00253, Product of P truncation <=0.001=0.00069. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
NCAPD3	In BD:Smallest P-value per gene=0.01537, Product of P truncation <=0.01=0.00245, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
FBXO38	In BD:Smallest P-value per gene=0.00032, Product of P truncation <=0.01=0.00032, Product of P truncation <=0.001=0.00052. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
HOXA3	In BP:Smallest P-value per gene=0.00034, Product of P truncation <=0.01=0.00034, Product of P truncation <=0.001=0.00034. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
MYL12B	In BD:Smallest P-value per gene=0.00246, Product of P truncation <=0.01=0.01078, Product of P truncation <=0.001=0.00246. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
MYL12A	In BD:Smallest P-value per gene=0.01437, Product of P truncation <=0.01=0.00678, Product of P truncation <=0.001=NA. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
THSD7A	In BP:Smallest P-value per gene=0.02421, Product of P truncation <=0.01=0.00032, Product of P truncation <=0.001=0.00425. It showed evidence for association with BD. It showed evidence for association with BD.	Positive
FLVCR2	In BP:Smallest P-value per gene=0.00053, Product of P truncation <=0.01=0.00001, Product of P truncation <=0.001=0.00035. It showed evidence for association with BD. It showed evidence for association with BD.	Positive

Genetic factors reported by this study for SZ and/or MDD

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	CAPN10	It showed no evidence for association with SZ.	Negative
SZ	LRRC36	It showed no evidence for association with SZ.	Negative
SZ	SEMG2	In SZ:Smallest P-value per gene=0.00387, Product of P truncation <=0.01=0.00387, Product of P truncation <=0.001=NA It showed evidence for association with SZ.	Positive
SZ	ANKRD35	It showed no evidence for association with SZ.	Negative
SZ	FLVCR2	It showed no evidence for association with SZ.	Negative
SZ	KLHDC1	It showed no evidence for association with SZ.	Negative
SZ	CPB2	It showed no evidence for association with SZ.	Negative
SZ	WDFY2	In SZ:Smallest P-value per gene=0.01216, Product of P truncation <=0.01=0.0046, Product of P truncation <=0.001=NA It showed evidence for association with SZ.	Positive
SZ	FABP3	It showed no evidence for association with SZ.	Negative
SZ	POLE2	It showed no evidence for association with SZ.	Negative
SZ	TMEM108	In SZ:Smallest P-value per gene=0.00038, Product of P truncation <=0.01=0.00006, Product of P truncation <=0.001=0.00007 It showed evidence for association with SZ.	Positive
SZ	PTPRE	It showed no evidence for association with SZ.	Negative
SZ	CDKN2A	In SZ:Smallest P-value per gene=0.00132, Product of P truncation <=0.01=0.00132, Product of P truncation <=0.001=NA It showed evidence for association with SZ.	Positive
SZ	DPP10	It showed no evidence for association with SZ.	Negative
SZ	PSKH1	In SZ:Smallest P-value per gene=0.00777, Product of P truncation <=0.01=0.00777, Product of P truncation <=0.001=NA It showed evidence for association with SZ.	Positive
SZ	PTGR2	It showed no evidence for association with SZ.	Negative
SZ	CSF2RB	It showed no evidence for association with SZ.	Negative
SZ	ZNF490	It showed no evidence for association with SZ.	Negative
SZ	TCAF1	It showed no evidence for association with SZ.	Negative
SZ	TDRD9	It showed no evidence for association with SZ.	Negative
SZ	ZNF274	It showed no evidence for association with SZ.	Negative
SZ	THSD7A	It showed no evidence for association with SZ.	Negative
SZ	ZNF284	It showed no evidence for association with SZ.	Negative
SZ	INTS6	In SZ:Smallest P-value per gene=0.00079, Product of P truncation <=0.01=0.00039, Product of P truncation <=0.001=0.00023 It showed evidence for association with SZ.	Positive
SZ	LRR1	It showed no evidence for association with SZ.	Negative
SZ	SVEP1	It showed no evidence for association with SZ.	Negative
SZ	CMTM8	It showed no evidence for association with SZ.	Negative
SZ	MYL12A	In SZ:Smallest P-value per gene=0.00106, Product of P truncation <=0.01=0.00096, Product of P truncation <=0.001=0.00124 It showed evidence for association with SZ.	Positive
SZ	TLE4	It showed no evidence for association with SZ.	Negative
SZ	PBRM1	In SZ:Smallest P-value per gene=0.00107, Product of P truncation <=0.01=0.00082, Product of P truncation <=0.001=0.00063 It showed evidence for association with SZ.	Positive
SZ	FBXO38	In SZ:Smallest P-value per gene=0.00456, Product of P truncation <=0.01=0.0053, Product of P truncation <=0.001=NA It showed evidence for association with SZ.	Positive
SZ	JAM3	In SZ:Smallest P-value per gene=0.00396, Product of P truncation <=0.01=0.00213, Product of P truncation <=0.001=0.00112 It showed evidence for association with SZ.	Positive
SZ	PFN4	In SZ:Smallest P-value per gene=0.00045, Product of P truncation <=0.01=0.00045, Product of P truncation <=0.001=0.00045 It showed evidence for association with SZ.	Positive
SZ	HOXA3	It showed no evidence for association with SZ.	Negative
SZ	AKAP10	It showed no evidence for association with SZ.	Negative
SZ	ATP6V0D1	It showed no evidence for association with SZ.	Negative
SZ	C10orf120	In SZ:Smallest P-value per gene=0.00583, Product of P truncation <=0.01=0.00591, Product of P truncation <=0.001=NA It showed evidence for association with SZ.	Positive
SZ	GNL3	In SZ:Smallest P-value per gene=0.00812, Product of P truncation <=0.01=0.00819, Product of P truncation <=0.001=NA It showed evidence for association with SZ.	Positive
SZ	LAMP3	It showed no evidence for association with SZ.	Negative
SZ	MCM3AP-AS1	It showed no evidence for association with SZ.	Negative
SZ	GLT8D1	In SZ:Smallest P-value per gene=0.00608, Product of P truncation <=0.01=0.00608, Product of P truncation <=0.001=NA It showed evidence for association with SZ.	Positive
SZ	NCAPD3	In SZ:Smallest P-value per gene=0.00135, Product of P truncation <=0.01=0.00064, Product of P truncation <=0.001=0.00137 It showed evidence for association with SZ.	Positive
SZ	TP53I3	In SZ:Smallest P-value per gene=0.00028, Product of P truncation <=0.01=0.00028, Product of P truncation <=0.001=0.00028 It showed evidence for association with SZ.	Positive
SZ	SIGLEC6	It showed no evidence for association with SZ.	Negative
SZ	DFNB31	It showed no evidence for association with SZ.	Negative
SZ	ITIH3	In SZ:Smallest P-value per gene=0.0005, Product of P truncation <=0.01=0.0005, Product of P truncation <=0.001=0.0005 It showed evidence for association with SZ.	Positive
SZ	CACNA1C	It showed no evidence for association with SZ.	Negative
SZ	RNPEPL1	It showed no evidence for association with SZ.	Negative
SZ	PALB2	It showed no evidence for association with SZ.	Negative
SZ	RSRC2	It showed no evidence for association with SZ.	Negative
SZ	MYL12B	In SZ:Smallest P-value per gene=0.00022, Product of P truncation <=0.01=0.01111, Product of P truncation <=0.001=0.00129 It showed evidence for association with SZ.	Positive
SZ	NEK4	In SZ:Smallest P-value per gene=0.00199, Product of P truncation <=0.01=0.00196, Product of P truncation <=0.001=0.00199 It showed evidence for association with SZ.	Positive