Study Report

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Basic Info

Reference	Green, E. K.,2012 PMID: 23070075
Citation	Green, E. K., M. Hamshere, et al. (2012). "Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case-control sample." Mol Psychiatry.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	1218 bipolar disorder (BD) cases and 2913 controls
SNP/Region/Marker Size	192,402 SNPs
Predominant Ethnicity	Caucasian
Population	British

Detail Info

Sample Diagnosis	DSM
Sample Status	All the participants in these studies were unrelated, white, living in the British Isles and were of European descent.
Technique	custom Illumina Infinium HD genotyping array
Statistical Method	chi-square tests
Result Summary	We report support for two of the three most strongly associated chromosomal regions in the Ferreira study, CACNA1C (rs1006737, P=4.09 x 10(-4)) and 15q14 (rs2172835, P=0.043) but not ANK3 (rs10994336, P=0.912). We have combined our ImmunoChip data (569 quasi-independent SNPs from the 3016 SNPs genotyped) with the recently published PGC-BD meta-analysis data, using either the PGC-BD combined discovery and replication data where available or just the discovery data where the SNP was not typed in a replication sample in PGC-BD. Our data provide support for two regions, at ODZ4 and CACNA1C, with prior evidence for genome-wide significant (GWS) association in PGC-BD meta-analysis. In addition, the combined analysis shows two novel GWS associations. First, rs7296288 (P=8.97 x 10(-9), odds ratio (OR)=0.9), an intergenic polymorphism on chromosome 12 located between RHEBL1 and DHH. Second, rs3818253 (P=3.88 x 10(-8), OR=1.16), an intronic SNP on chromosome 20q11.2 in the gene TRPC4AP, which lies in a high linkage disequilibrium region along with the genes GSS and MYH7B.

SNPs reported by this study for BD (count: 27)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs3818253	TRPC4AP	A/G	BD ImmunoChip:P-value = 0.00000265,OR = 1.333;ImmunoChip, PGC-BD combined data:P-balue = 0.0000000388,OR = 1.164	The SNP showed a significant association with BD. The SNP showed a significant association with BD.	Positive
rs3845817		C/T	BD ImmunoChip:P-value = 0.309,OR = 0.951;ImmunoChip, PGC-BD combined data:P-balue = 0.00000145,OR = 0.915	Suggestive association was found. Suggestive association was found.	Trend
rs263906		C/T	BD ImmunoChip:P-value = 0.545,OR = 1.034;ImmunoChip, PGC-BD combined data:P-balue = 0.000483,OR = 1.074	No significant association was observed. No significant association was observed.	Negative
rs3755806	PBRM1	C/T	BD ImmunoChip:P-value = 0.0222,OR = 0.891;ImmunoChip, PGC-BD combined data:P-balue = 0.000000421,OR = 0.889	Suggestive association was found. Suggestive association was found.	Trend
rs2273684	GSS	G/T	BD ImmunoChip:P-value = 0.00000923,OR = 1.245;ImmunoChip, PGC-BD combined data:P-balue = 0.000000472,OR = 1.119	Suggestive association was found. Suggestive association was found.	Trend
rs2287921	RASIP1	C/T	BD ImmunoChip:P-value = 0.059,OR = 1.098;ImmunoChip, PGC-BD combined data:P-balue = 0.000000285,OR = 1.1	Suggestive association was found. Suggestive association was found.	Trend
rs12912251	C15orf53	G/T	BD ImmunoChip:P-value = 0.029,OR = 1.125;ImmunoChip, PGC-BD combined data:P-balue = 0.000000294,OR = 1.103	Suggestive association was found. Suggestive association was found.	Trend
rs16966413	SPRED1	A/G	BD ImmunoChip:P-value = 0.015,OR = 0.824;ImmunoChip, PGC-BD combined data:P-balue = 0.00000593,OR = 0.872	Suggestive association was found. Suggestive association was found.	Trend
rs12576775	TENM4	A/G	BD ImmunoChip:P-value = 0.047,OR = 0.887;ImmunoChip, PGC-BD combined data:P-balue = 0.0000000062,OR = 0.881	The SNP showed a significant association with BD. The SNP showed a significant association with BD.	Positive
rs1274726	LMBR1L	C/T	BD ImmunoChip:P-value = 0.082,OR = 1.09;ImmunoChip, PGC-BD combined data:P-balue = 0.00000148,OR = 1.121	Suggestive association was found. Suggestive association was found.	Trend
rs10994397	ANK3	C/T	BD ImmunoChip:P-value = 0.923,OR = 1.01;ImmunoChip, PGC-BD combined data:P-balue = 0.00000215,OR = 0.842	Suggestive association was found. Suggestive association was found.	Trend
rs11085829	NFIX	A/G	BD ImmunoChip:P-value = 0.98,OR = 1.001;ImmunoChip, PGC-BD combined data:P-balue = 0.000249,OR = 0.931	No significant association was observed. No significant association was observed.	Negative
rs1006737	CACNA1C	A/G	BD ImmunoChip:P-value = 0.000409,OR = 1.198;ImmunoChip, PGC-BD combined data:P-balue = 0.000000216,OR = 1.128	Suggestive association was found. Suggestive association was found.	Trend
rs9834970	TRANK1 LRBA	T/C	BD ImmunoChip:P-value = 0.0519,OR = 0.91;ImmunoChip, PGC-BD combined data:P-balue = 0.00000304,OR = 0.901	Suggestive association was found. Suggestive association was found.	Trend
rs9804190	ANK3	C/T	BD ImmunoChip:P-value = 0.682,OR = 0.977;ImmunoChip, PGC-BD combined data:P-balue = 0.000736,OR = 1.08	No significant association was observed. No significant association was observed.	Negative
rs7578035		G/T	BD ImmunoChip:P-value = 0.532,OR = 1.031;ImmunoChip, PGC-BD combined data:P-balue = 0.00000413,OR = 1.083	Suggestive association was found. Suggestive association was found.	Trend
rs736408	ITIH3	C/T	BD ImmunoChip:P-value = 0.0756,OR = 1.098;ImmunoChip, PGC-BD combined data:P-balue = 0.000000503,OR = 1.1	Suggestive association was found. Suggestive association was found.	Trend
rs9371601	SYNE1	G/T	BD ImmunoChip:P-value = 0.0764,OR = 0.916;ImmunoChip, PGC-BD combined data:P-balue = 0.000000138,OR = 0.911	Suggestive association was found. Suggestive association was found.	Trend
rs875326	TNR	C/T	BD ImmunoChip:P-value = 0.378,OR = 0.945;ImmunoChip, PGC-BD combined data:P-balue = 0.00105,OR = 1.078	No significant association was observed. No significant association was observed.	Negative
rs6550435	TRANK1	G/T	BD ImmunoChip:P-value = 0.819,OR = 0.988;ImmunoChip, PGC-BD combined data:P-balue = 0.0000454,OR = 1.077	Suggestive association was found. Suggestive association was found.	Trend
rs6102947	PTPRT	C/G	BD ImmunoChip:P-value = 0.2562,OR = 1.189;ImmunoChip, PGC-BD combined data:P-balue = 0.0000513,OR = 1.289	Suggestive association was found. Suggestive association was found.	Trend
rs7296288	DHH	A/C	BD ImmunoChip:P-value = 0.055,OR = 0.912;ImmunoChip, PGC-BD combined data:P-balue = 0.00000000897,OR = 0.902	The SNP showed a significant association with BD. The SNP showed a significant association with BD.	Positive
rs6746896	LMAN2L CNNM4	A/G	BD ImmunoChip:P-value = 0.011,OR = 1.146;ImmunoChip, PGC-BD combined data:P-balue = 0.000000114,OR = 1.106	Suggestive association was found. Suggestive association was found.	Trend
rs4332037	MAD1L1	C/T	BD ImmunoChip:P-value = 0.739,OR = 1.022;ImmunoChip, PGC-BD combined data:P-balue = 0.0000429,OR = 0.914	No significant association was observed. No significant association was observed.	Negative
rs3968	HNRNPA1P41	C/G	BD ImmunoChip:P-value = 0.3809,OR = 1.055;ImmunoChip, PGC-BD combined data:P-balue = 0.0125,OR = 1.041	No significant association was observed. No significant association was observed.	Negative
rs4765913	CACNA1C	A/T	BD ImmunoChip:P-value = 0.0149,OR = 1.153;ImmunoChip, PGC-BD combined data:P-balue = 0.000000000978,OR = 1.142	The SNP showed a significant association with BD. The SNP showed a significant association with BD.	Positive
rs4668059	STK39	C/T	BD ImmunoChip:P-value = 0.731,OR = 1.026;ImmunoChip, PGC-BD combined data:P-balue = 0.00023,OR = 1.107	No significant association was observed. No significant association was observed.	Negative

Genes reported by this study for BD (count: 17)

Gene	Statistical Values/Author Comments	Result Category
TENM4	BD ImmunoChip:P-value = 0.047,OR = 0.887;ImmunoChip, PGC-BD combined data:P-balue = 0.0000000062,OR ...... BD ImmunoChip:P-value = 0.047,OR = 0.887;ImmunoChip, PGC-BD combined data:P-balue = 0.0000000062,OR = 0.881 The SNP showed a significant association with BD. More...	Positive
C15orf53	BD ImmunoChip:P-value = 0.029,OR = 1.125;ImmunoChip, PGC-BD combined data:P-balue = 0.000000294,OR =...... BD ImmunoChip:P-value = 0.029,OR = 1.125;ImmunoChip, PGC-BD combined data:P-balue = 0.000000294,OR = 1.103 Suggestive association was found. More...	Trend
ANK3	BD ImmunoChip:P-value = 0.923,OR = 1.01;ImmunoChip, PGC-BD combined data:P-balue = 0.00000215,OR = 0...... BD ImmunoChip:P-value = 0.923,OR = 1.01;ImmunoChip, PGC-BD combined data:P-balue = 0.00000215,OR = 0.842 Suggestive association was found. More...	Trend
GSS	BD ImmunoChip:P-value = 0.00000923,OR = 1.245;ImmunoChip, PGC-BD combined data:P-balue = 0.000000472...... BD ImmunoChip:P-value = 0.00000923,OR = 1.245;ImmunoChip, PGC-BD combined data:P-balue = 0.000000472,OR = 1.119 Suggestive association was found. More...	Trend
PBRM1	BD ImmunoChip:P-value = 0.0222,OR = 0.891;ImmunoChip, PGC-BD combined data:P-balue = 0.000000421,OR ...... BD ImmunoChip:P-value = 0.0222,OR = 0.891;ImmunoChip, PGC-BD combined data:P-balue = 0.000000421,OR = 0.889 Suggestive association was found. More...	Trend
MAD1L1	BD ImmunoChip:P-value = 0.739,OR = 1.022;ImmunoChip, PGC-BD combined data:P-balue = 0.0000429,OR = 0...... BD ImmunoChip:P-value = 0.739,OR = 1.022;ImmunoChip, PGC-BD combined data:P-balue = 0.0000429,OR = 0.914 No significant association was observed. More...	Negative
PTPRT	BD ImmunoChip:P-value = 0.2562,OR = 1.189;ImmunoChip, PGC-BD combined data:P-balue = 0.0000513,OR = ...... BD ImmunoChip:P-value = 0.2562,OR = 1.189;ImmunoChip, PGC-BD combined data:P-balue = 0.0000513,OR = 1.289 Suggestive association was found. More...	Trend
SPRED1	BD ImmunoChip:P-value = 0.015,OR = 0.824;ImmunoChip, PGC-BD combined data:P-balue = 0.00000593,OR = ...... BD ImmunoChip:P-value = 0.015,OR = 0.824;ImmunoChip, PGC-BD combined data:P-balue = 0.00000593,OR = 0.872 Suggestive association was found. More...	Trend
CACNA1C	SNPs in CACNA1C were significantly associated with BD. SNPs in CACNA1C were significantly associated with BD.	Positive
LMBR1L	BD ImmunoChip:P-value = 0.082,OR = 1.09;ImmunoChip, PGC-BD combined data:P-balue = 0.00000148,OR = 1...... BD ImmunoChip:P-value = 0.082,OR = 1.09;ImmunoChip, PGC-BD combined data:P-balue = 0.00000148,OR = 1.121 Suggestive association was found. More...	Trend
TRANK1	BD ImmunoChip:P-value = 0.819,OR = 0.988;ImmunoChip, PGC-BD combined data:P-balue = 0.0000454,OR = 1...... BD ImmunoChip:P-value = 0.819,OR = 0.988;ImmunoChip, PGC-BD combined data:P-balue = 0.0000454,OR = 1.077 Suggestive association was found. More...	Trend
SYNE1	BD ImmunoChip:P-value = 0.0764,OR = 0.916;ImmunoChip, PGC-BD combined data:P-balue = 0.000000138,OR ...... BD ImmunoChip:P-value = 0.0764,OR = 0.916;ImmunoChip, PGC-BD combined data:P-balue = 0.000000138,OR = 0.911 Suggestive association was found. More...	Trend
TNR	BD ImmunoChip:P-value = 0.378,OR = 0.945;ImmunoChip, PGC-BD combined data:P-balue = 0.00105,OR = 1.0...... BD ImmunoChip:P-value = 0.378,OR = 0.945;ImmunoChip, PGC-BD combined data:P-balue = 0.00105,OR = 1.078 No significant association was observed. More...	Negative
LRBA	BD ImmunoChip:P-value = 0.0519,OR = 0.91;ImmunoChip, PGC-BD combined data:P-balue = 0.00000304,OR = ...... BD ImmunoChip:P-value = 0.0519,OR = 0.91;ImmunoChip, PGC-BD combined data:P-balue = 0.00000304,OR = 0.901 Suggestive association was found. More...	Trend
TRPC4AP	BD ImmunoChip:P-value = 0.00000265,OR = 1.333;ImmunoChip, PGC-BD combined data:P-balue = 0.000000038...... BD ImmunoChip:P-value = 0.00000265,OR = 1.333;ImmunoChip, PGC-BD combined data:P-balue = 0.0000000388,OR = 1.164 The SNP showed a significant association with BD. More...	Positive
NFIX	BD ImmunoChip:P-value = 0.98,OR = 1.001;ImmunoChip, PGC-BD combined data:P-balue = 0.000249,OR = 0.9...... BD ImmunoChip:P-value = 0.98,OR = 1.001;ImmunoChip, PGC-BD combined data:P-balue = 0.000249,OR = 0.931 No significant association was observed. More...	Negative
STK39	BD ImmunoChip:P-value = 0.731,OR = 1.026;ImmunoChip, PGC-BD combined data:P-balue = 0.00023,OR = 1.1...... BD ImmunoChip:P-value = 0.731,OR = 1.026;ImmunoChip, PGC-BD combined data:P-balue = 0.00023,OR = 1.107 No significant association was observed. More...	Negative