Study Report

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Basic Info

Reference	Pisanu, C., 2013 PMID: 24126189
Citation	Pisanu, C., D. Congiu, et al. (2013). "No association of endocannabinoid genes with bipolar disorder or lithium response in a Sardinian sample." Psychiatry Res 210(3): 887-890.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	291 BD type I and 66 BD type II patients, and 422 controls
SNP/Region/Marker Size	25 SNPs
Predominant Ethnicity	Caucasian
Population	Sardinian
Gender	134 male and 223 female cases, 217 male and 205 female controls
Age Group	adults : mean age=44.09, SD=14.35 years of cases, mean age=42, SD=14.21 years of controls

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	Cases comprised 291 BD type I and 66 BD type II patients diagnosed by trained clinical psychopharmaco logists according to DSM-IV criteria and the Schedule for Affective Disorder and Schizophrenia-Life time Version (SADS-L). Of the 357 patients, 204 were characterized for lithium response using the 'Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder' as described previously. Age at onset of patients, mean age=26.29, SD=10.41 years.
Technique	genotyped with the Kaspar method
Statistical Method	Differences in demographic variables between cases and controls were evaluated with t-test or chi-square(_2) test. Deviation from the Hardy-Weinberg equilibrium (HWE) was tested with _2 test. As gender distribution significantly differed between cases and controls, the genotypic association analysis was tested using logistic regression under the additive model with sex as a covariate. All p values were adjusted for multiple comparisons by permutation test with 10,000 permutations. All the analyses were carried out with PLINK, version 2.07 and Haploview.
Result Summary	No significant association was reported for FAAH or CNR1. SNPs rs11487077 and rs6465903 in NAPE-PLD showed nominal association (p=0.033 and p=0.026, respectively) with BD, not significant after permutation testing. These SNPs were also tested for association with lithium response in 204 BD patients characterized for response to long-term lithium treatment, reporting no significant findings. As a whole, our results do not support a clear role of FAAH, CNR1 and NAPE-PLD in BD and lithium response. Additional studies on independent, larger samples are warranted to further explore the involvement of the eCB system in BD.

SNPs reported by this study for BD (count: 23)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs806376	CNR1	C/T	logistic regression, P-value=0.316, OR=0.9	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs806375	CNR1	T/A	logistic regression, P-value=0.37, OR=0.91	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs806374	CNR1	C/T	logistic regression, P-value=0.25, OR=1.13	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs1049353	CNR1	A/G	logistic regression, P-value=0.385, OR=0.89	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs12720071	CNR1	G/A	logistic regression, P-value=0.818, OR=1.03	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs806368	CNR1	G/A	logistic regression, P-value=0.447, OR=1.09	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs806366	CNR1	T/C	logistic regression, P-value=0.833, OR=0.98	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs7766029	CNR1	C/T	logistic regression, P-value=0.552, OR=0.94	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs7789727	NAPEPLD	A/G	logistic regression, P-value=0.581, OR=1.21	Logistic regression analysis showed nominal association betw...... Logistic regression analysis showed nominal association between rs6465903 located in NAPE-PLD and BD, but not with lithium response. Separating the samples into two groups of BDI and BDII showed that these two SNPs were nominally associated with BDI but not with BDII. However, odds ratio (OR) was not significantly increased in comparison to the whole sample (SNP rs6465903,OR=1.42 in the whole sample and 1.44 in the BDI sample). More...	Negative
rs6465903	NAPEPLD	A/C	logistic regression, P-value=0.026, OR=1.42	Nominal association with BD or lithium response was not obse...... Nominal association with BD or lithium response was not observed in this study. More...	Positive
rs12540583	NAPEPLD	C/A	logistic regression, P-value=0.7, OR=0.92	Nominal association with BD or lithium response was not obse...... Nominal association with BD or lithium response was not observed in this study. More...	Negative
rs11487077	NAPEPLD	C/A	logistic regression, P-value=0.033, OR=1.55	Logistic regression analysis showed nominal association betw...... Logistic regression analysis showed nominal association between rs11487077 located in NAPE-PLD and BD, but not with lithium response. Separating the samples into two groups of BDI and BDII showed that these two SNPs were nominally associated with BDI but not with BDII. However, odds ratio (OR) was not significantly increased in comparison to the whole sample (SNPrs11487077, OR=1.55 in the whole sample and 1.63 in the BDI sample). More...	Positive
rs17605251	NAPEPLD	G/A	logistic regression, P-value=0.337, OR=0.87	Nominal association with BD or lithium response was not obse...... Nominal association with BD or lithium response was not observed in this study. More...	Negative
rs806380	CNR1	G/A	logistic regression, P-value=0.757, OR=0.97	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs9450898	CNR1	T/C	logistic regression, P-value=0.176, OR=0.83	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs6454672	CNR1	C/T	logistic regression, P-value=0.268, OR=0.85	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs17361936	FAAH	T/C	logistic regression, P-value=0.855, OR=1.02	None of the SNPs of FAAH showed nominal association with BD ...... None of the SNPs of FAAH showed nominal association with BD or lithium response. More...	Negative
rs4141964	FAAH	A/G	logistic regression, P-value=0.677, OR=0.95	None of the SNPs of FAAH showed nominal association with BD ...... None of the SNPs of FAAH showed nominal association with BD or lithium response. More...	Negative
rs6429600	FAAH	G/A	logistic regression, P-value=0.21, OR=0.84	None of the SNPs of FAAH showed nominal association with BD ...... None of the SNPs of FAAH showed nominal association with BD or lithium response. More...	Negative
rs324419	FAAH	A/G	logistic regression, P-value=0.749, OR=1.04	None of the SNPs of FAAH showed nominal association with BD ...... None of the SNPs of FAAH showed nominal association with BD or lithium response. More...	Negative
rs324420	FAAH	A/C	logistic regression, P-value=0.218, OR=0.83	None of the SNPs of FAAH showed nominal association with BD ...... None of the SNPs of FAAH showed nominal association with BD or lithium response. More...	Negative
rs806365	CNR1	C/T	logistic regression, P-value=0.946, OR=0.99	None of the SNPs of CNR1 showed nominal association with BD ...... None of the SNPs of CNR1 showed nominal association with BD or lithium response. More...	Negative
rs11576941	FAAH	T/G	logistic regression, P-value=0.793, OR=1.03	None of the SNPs of FAAH showed nominal association with BD ...... None of the SNPs of FAAH showed nominal association with BD or lithium response. More...	Negative

Haplotypes reported by this study for BD (count: 6)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs11487077 - rs6465903 - rs13232194 - rs17605251 - rs12540583	T-A-A-A-A	NAPEPLD	P-value=0.611, X<sup>2</sup>=0.26	It showed no nominal association with BD. It showed no nominal association with BD.	Negative
rs11487077 - rs6465903 - rs13232194 - rs17605251 - rs12540583	T-A-A-A-C	NAPEPLD	P-value=0.883, X<sup>2</sup>=0.02	It showed no nominal association with BD. It showed no nominal association with BD.	Negative
rs11487077 - rs6465903 - rs13232194 - rs17605251 - rs12540583	T-A-C-A-A	NAPEPLD	P-value=0.011, X<sup>2</sup>=6.42	Of the 6 possible combinations of NAPE-PLD, only haplotype T...... Of the 6 possible combinations of NAPE-PLD, only haplotype TACAA showed nominal association with BD, but not with lithium response. More...	Positive
rs11487077 - rs6465903 - rs13232194 - rs17605251 - rs12540583	T-A-A-C-C	NAPEPLD	P-value=0.379, X<sup>2</sup>=0.78	It showed no nominal association with BD. It showed no nominal association with BD.	Negative
rs11487077 - rs6465903 - rs13232194 - rs17605251 - rs12540583	A-A-A-A-C	NAPEPLD	P-value=0.742, X<sup>2</sup>=0.11	It showed no nominal association with BD. It showed no nominal association with BD.	Negative
rs11487077 - rs6465903 - rs13232194 - rs17605251 - rs12540583	A-G-A-A-C	NAPEPLD	P-value=0.227, X<sup>2</sup>=1.46	It showed no nominal association with BD. It showed no nominal association with BD.	Negative

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs13232194	NAPEPLD		T/A		logistic regression, P-value=0.232, OR=1.16	Nominal association with BD or lithium response was not obse...... Nominal association with BD or lithium response was not observed in this study. More...	Negative

Genes reported by this study for BD (count: 3)

Gene	Statistical Values/Author Comments	Result Category
NAPEPLD	As a whole, our results do not support a clear role of NAPE-PLD in BD and lithium response. As a whole, our results do not support a clear role of NAPE-PLD in BD and lithium response.	Positive
CNR1	As a whole, our results do not support a clear role of CNR1 in BD and lithium response. As a whole, our results do not support a clear role of CNR1 in BD and lithium response.	Negative
FAAH	As a whole, our results do not support a clear role of FAAH in BD and lithium response. As a whole, our results do not support a clear role of FAAH in BD and lithium response.	Negative