Study Report

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Basic Info

Reference	Djurovic, S.,2010 PMID: 20451256
Citation	Djurovic, S., O. Gustafsson, et al. (2010). "A genome-wide association study of bipolar disorder in Norwegian individuals, followed by replication in Icelandic sample." J Affect Disord 126(1-2): 312-316.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Genome-wide association study
Sample Size	Norwegian sample including patienst with bipolar disorder (n=194), healthy controls (n=336) and patients with schizophrenia (n=230)
SNP/Region/Marker Size	620,390 SNPs
Predominant Ethnicity	Caucasian
Population	Norwegian and Icelander

Detail Info

Sample Diagnosis	DSM
Sample Status	The Oslo TOP study (discovery sample):In order to participate in the current study subjects needed to be between 18 and 65 years, obtain an IQ score of above 70, meet the DSM-IV criteria for SCZ and BD,and be willing and able to give informed consent.For more details about recruitment procedure,see Larsson et al., 2009.The healthy controls subjects have been previously described (Athanasiu et al., 2010). Healthy subjects were excluded if they or any of their close relatives had a lifetime history of a severe psychiatric disorder (SCZ,BD and major depression), a history of medical problems thought to interfere with brain function (hypothyroidism,uncontrolled hypertension and diabetes), or significant illicit drug use (diagnosis of abuse or dependency).Iceland sample (replication sample):Patients and controls were recruited from all over Iceland.The controls were recruited as a part of various genetic programs at deCODE and were not screened for psychiatric disorders.
Replication Size	Icelandic sample of patients with bipolar disorder (n=435), and healthy controls (n=10,258)
Technique	genotyping(Affymetrix and Illumina)
Statistical Method	The TOP discovery sample was analyzed for SNP-association using an allelic test implemented in PLINK (Purcell et al.,2007). Association analyses in the Icelandic replication sample were undertaken using a Fisher exact allelic test.We undertook a combined analysis using the weighted Stouffer's z method for combining P values (Whitlock, M.C.,2005).
Result Summary	We selected 1000 markers with the lowest P values in the TOP discovery GWAS and tested these (or their surrogates) for association in the Icelandic replication sample. Polymorphisms on 35 loci were confirmed associated with bipolar disorder (nominal P value<0.05; not corrected for multiple testing) in the replication sample. The most significant markers were located in DLEU2, GUCY1B2, PKIA, CCL2, CNTNAP5, DPP10, and FBN1. The combined group of schizophrenia and bipolar disorder compared to controls did not provide additional significant findings. We detected weak but reproducible association with markers in several genes, in proximity to susceptibility loci found in previous GWAS studies of bipolar disorder. Further work is required to study their localization, expression, and regulation and international meta-analytic efforts will help to further elucidate their role.

SNPs reported by this study for BD (count: 49)

SNP	Related Gene(s)	Statistical Values	Author Comments	Result Category
rs11080256	CCL2	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000356, OR=1.6	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11617400	GUCY1B2	Combined analysis: for TOP Norway (discovery sample): P-value = 0.0000373, OR=1.8	Suggestive association was found(P-values ranging from 5.39E...... Suggestive association was found(P-values ranging from 5.39E-07 to 9.95E-05). More...	Trend
rs10901040	DPP6 ZXDC	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001021, OR=0.605	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4714904	RCAN2	Combined analysis: J4for Iceland (replication sample): P-value = 0.017415, OR=1.2, Stouffer's z value=0.0006	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4960568	DPP6	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001413, OR=0.61	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs6679053	PLD5	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001034, OR=1.64; for Iceland (replication sample): P-value = 0.022069, OR=1.2, Stouffer's z value=0.001	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7081438	PCDH15	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001217, OR=0.655	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4257412	DDX18	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000844, OR=0.64	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4328493	CCL2	Combined analysis: for Iceland (replication sample): P-value = 0.016864, OR=1.17, Stouffer's z value=0.0004	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs447981	SLC14A1	Combined analysis: J4for Iceland (replication sample): P-value = 0.009733, OR=1.2, Stouffer's z value=0.0003	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs448245	PKIA	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001219, OR=1.53	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs264826	PKIA	Combined analysis: for TOP Norway (discovery sample): P-value = 0.00061, OR=1.53; for Iceland (replication sample): P-value = 0.044268, OR=1.15, Stouffer's z value=0.0021	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2699365	CNTNAP5	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001447, OR=0.65	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2901197	CNTNAP5	Combined analysis: for Iceland (replication sample): P-value = 0.016798, OR=1.18, Stouffer's z value=0.0008	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs423804	NRIP1	Combined analysis: J4for Iceland (replication sample): P-value = 0.040931, OR=0.78, Stouffer's z value=0.0024	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1848053	FBN1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000565, OR=0.59	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1979601	DPP6	Combined analysis: J4for Iceland (replication sample): P-value = 0.044684, OR=0.86, Stouffer's z value=0.0029	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2420559	CNTNAP5	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001396, OR=0.65	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2578121	LINC00856	Combined analysis: for TOP Norway (discovery sample): P-value = 0.00043, OR=1.57	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1750567	DLEU1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.0000223, OR=0.58; for Iceland (replication sample): P-value = 0.003594, OR=0.82, Stouffer's z value=0.0000212	Suggestive association was found(P-values ranging from 5.39E...... Suggestive association was found(P-values ranging from 5.39E-07 to 9.95E-05). More...	Trend
rs1750565	DLEU1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.0000236, OR=0.58	Suggestive association was found(P-values ranging from 5.39E...... Suggestive association was found(P-values ranging from 5.39E-07 to 9.95E-05). More...	Trend
rs1798972	DLEU1 ST13P4	Combined analysis: for Iceland (replication sample): P-value = 0.003414, OR=0.82, Stouffer's z value=0.0000188	Suggestive association was found(P-values ranging from 5.39E...... Suggestive association was found(P-values ranging from 5.39E?07 to 9.95E?05). More...	Trend
rs1798968	DLEU1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.0000274, OR=0.58	Suggestive association was found(P-values ranging from 5.39E...... Suggestive association was found(P-values ranging from 5.39E-07 to 9.95E-05). More...	Trend
rs1529289	CNTNAP5	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001187, OR=0.64	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1510122	PKIA	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000779, OR=1.57; for Iceland (replication sample): P-value = 0.004653, OR=1.22, Stouffer's z value=0.0001	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1567426	SLC14A1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000524, OR=1.57	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1566816	FBN1	Combined analysis: for Iceland (replication sample): P-value = 0.027362, OR=0.84, Stouffer's z value=0.001	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs13216050	RCAN2	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000664, OR=1.85	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1292735	NRIP1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001239, OR=0.46	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1472779	DDX18	Combined analysis: J4for Iceland (replication sample): P-value = 0.012295, OR=0.85, Stouffer's z value=0.0004	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1435961	LINC00856	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000994, OR=1.53; for Iceland (replication sample): P-value = 0.009807, OR=0.84, Stouffer's z value=0.0004; for Iceland (replication sample): P-value = 0.009409, OR=0.84, Stouffer's z value=0.0002	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11658512	CCL2	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000438, OR=1.59	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11652429	CCL2	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000294, OR=1.61	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs12052834	DDX18	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000734, OR=0.64; for Iceland (replication sample): P-value = 0.007834, OR=0.83, Stouffer's z value=0.0002	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11992953	CPQ	Combined analysis: J4for Iceland (replication sample): P-value = 0.048143, OR=0.73, Stouffer's z value=0.0029	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs9527256		Combined analysis: for TOP Norway (discovery sample): P-value = 0.001506, OR=0.66; for Iceland (replication sample): P-value = 0.024485, OR=1.17, Stouffer's z value=0.0013	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs931781	FBN1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000937, OR=0.61	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs825795	PCDH15	Combined analysis: for Iceland (replication sample): P-value = 0.012669, OR=1.18, Stouffer's z value=0.0004	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs809846	DLEU1 ST13P4	Combined analysis: for TOP Norway (discovery sample): P-value = 0.0000317, OR=0.58	Suggestive association was found(P-values ranging from 5.39E...... Suggestive association was found(P-values ranging from 5.39E-07 to 9.95E-05). More...	Trend
rs8042197	FBN1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000478, OR=0.59	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs8026561	SLCO3A1	Combined analysis: J4for Iceland (replication sample): P-value = 0.037693, OR=0.85, Stouffer's z value=0.0023	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7844514	CPQ	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001124, OR=2.45	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs753950	GRIN2B	Combined analysis: J4for Iceland (replication sample): P-value = 0.026437, OR=1.18, Stouffer's z value=0.0013	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7317089	GUCY1B2	Combined analysis: J4for Iceland (replication sample): P-value = 0.003839, OR=0.8, Stouffer's z value=0.0000264	Suggestive association was found(P-values ranging from 5.39E...... Suggestive association was found(P-values ranging from 5.39E-07 to 9.95E-05). More...	Trend
rs7310876	GRIN2B	Combined analysis: for TOP Norway (discovery sample): P-value = 0.001079, OR=1.56	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7184694		Combined analysis: for TOP Norway (discovery sample): P-value = 0.000251, OR=0.62; for Iceland (replication sample): P-value = 0.033829, OR=1.15, Stouffer's z value=0.001	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7183870	SLCO3A1	Combined analysis: for TOP Norway (discovery sample): P-value = 0.00151, OR=0.64	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7119726	SHANK2	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000944, OR=1.57; for Iceland (replication sample): P-value = 0.045061, OR=0.86, Stouffer's z value=0.0025	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7100273	PCDH15	Combined analysis: for TOP Norway (discovery sample): P-value = 0.000675, OR=0.64	No significant association was observed in BD. No significant association was observed in BD.	Negative

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

Gene	Statistical Values/Author Comments	Result Category
PCDH15	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
DDX18	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
PLD5	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
SLC14A1	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
SHANK2	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
SLCO3A1	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
CCL2	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
CPQ	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
FBN1	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
RCAN2	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
NRIP1	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
CNTNAP5	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
PKIA	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
GUCY1B2	Suggestive association of this gene was found(P-values ranging from 5.39E-07 to 9.95E-05). Suggestive association of this gene was found(P-values ranging from 5.39E-07 to 9.95E-05).	Trend
DPP6	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
ZXDC	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative
GRIN2B	No significant association of this gene was observed in BD. No significant association of this gene was observed in BD.	Negative