Study Report

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Basic Info

Reference	Maheshwari, M.,2009 PMID: 19194963
Citation	Maheshwari, M., J. Shi, et al. (2009). Common and rare variants of DAOA in bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 150B(7): 960-966.
Disease Type	Bipolar Disorder
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	Common SNP Association Tests:376 parent-offspring trios (parents plus one affected child) consisted of 335 bipolar disorder type I patients(BP-I) and 41 schizoaffective disorder bipolar type(SAB) patients;19 families with 146 samples in a subset of CNG pedigrees(52 BP-I and 20 BP-II);Rare Variant Association Test:555 unrelated bipolar patients(531 BP-I and 24 SAB) and 564 unrelated control subjects
SNP/Region/Marker Size	38 SNPs for Common SNP Association Test,8 SNPs for STatistical Explanation,53 SNPs for Rare Variant Association Test
Predominant Ethnicity	Caucasian
Gender	male/female: 157/219 in Common SNP Association Tests samples, in BD patients and 267/198 in controls;19/33 in BPI and 4/16 in BPII in a subset of CNG pedigrees;228/327 in BP and 282/282 in controls in Rare Variant Association Test samples

Detail Info

Sample Diagnosis	DSM
Sample Status	1.Common SNP Association Tests:Three hundred seventy-six parent-offspring trios (parents plus one affected child) were selected from three BP projects: the CNG project, the NIMH Genetics Initiative project, and the University of Chicago-Johns Hopkins-NIMH Intramural Program (CHIP). All participants were of European descent according to self-reported ancestry and further confirmed by a STRUCTURE [Pritchard et al.,2000] analysis using 254 unlinked SNPs (data not shown).Two hundred seventy-nine samples (24.7%) from 93 trios overlapped with the subjects tested in the original BP association study [Hattori et al., 2003]. To test whether any association underlies the previously observed linkage signals in the CNGsample set [Liu et al., 2001],In a subset of CNG pedigreeswe genotyped these eight SNPs in a subset ofCNGpedigrees. This sample set included 19 familieswith146 samples. Fifty-two individuals were diagnosed with BPI (33 females and 19 males), and 20 with BPII (16 females and 4 males).2.Rare Variant Association Test:A total of 555 unrelated bipolar patients were recruited for this study. Of them, five were from theCNGcollections [Berrettini et al.,1991], 478 fromtheNIMHGenetics Initiative waves 1-4 collections(http://www.nimhgenetics.org/) [Nurnberger et al., 1997; Dick et al., 2003], and 72 from the CHIP collection [Potash et al.,2007]. Ascertainment and diagnostic methods for participants from CNG, the NIMH waves 1-4 and the CHIP collections have been described in detail elsewhere [Berrettini et al., 1991; Nurnberger et al., 1997; Potash et al., 2007]. All individuals were of European ancestry based on self-reported ancestry and further confirmed by a STRUCTURE [Pritchard et al., 2000] analysis using 254 unlinked SNPs (data not shown).Five hundred sixty-four unrelated control subjects were selected from the NIMH Schizophrenia Genetics Initiative controls collection (http://www.nimhgenetics.org/, a list of the contributors to sample collection is shown in Acknowledgments Section). These control samples were all of European ancestry and free of major psychiatric disorders.
Technique	genotyping
Statistical Method	transmission disequilibrium tests (TDTs) for Common SNP Association Test and Explanation for Positional Cloning (STEPC)
Result Summary	One SNP rs1935058 could explain the linkage signal in the family sample set (P = 0.055) using STEPC analysis. No significant allelic association was detected in an association study by genotyping 38 common SNPs in 376 Caucasian BP trios. Resequencing identified 53 SNPs, of which 46 were novel SNPs. There was no significant excess of rare variants in cases relative to controls. Our results suggest that DAOA does not have a major effect on BP susceptibility. However, DAOA may contribute to bipolar susceptibility in some specific families as evidenced by the STEPC analysis.

SNPs reported by this study for BD (count: 39)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs978714	DAOA	A/G	TDT: Raw TDT P-value = 0.059, Adaptive permutation corrected P-value = 0.688	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs9558581	DAOA-AS1 DAOA	C/G	TDT: Raw TDT P-value = 0.451, Adaptive permutation corrected P-value = 0.875	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs9558551	DAOA	A/C	TDT: Raw TDT P-value = 0.697, Adaptive permutation corrected P-value = 0.438	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs954581	DAOA-AS1 DAOA	C/T	TDT: Raw TDT P-value = 0.313, Adaptive permutation corrected P-value = 1	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs9519683	DAOA DAOA-AS1	G/C	TDT: Raw TDT P-value = 0.143, Adaptive permutation corrected P-value = 0.429	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs9519671	DAOA	A/G	TDT: Raw TDT P-value = 0.054, Adaptive permutation corrected P-value = 0.938	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs947267	DAOA DAOA-AS1	A/C	TDT: Raw TDT P-value = 0.251, Adaptive permutation corrected P-value = 0.875	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs9301034	DAOA-AS1 DAOA	G/A	TDT: Raw TDT P-value = 0.17, Adaptive permutation corrected P-value = 0.429	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs9301030	DAOA DAOA-AS1	G/A	TDT: Raw TDT P-value = 0.145, Adaptive permutation corrected P-value = 0.476 STEPC: sib_tdt P-value = 0.031, TG P-value = 0.038	No significant allelic association with BP was found, but as...... No significant allelic association with BP was found, but association underlies the previously observed linkage signals in the CNGsample set was found. More...	Positive
rs9301029	DAOA	A/G	TDT: Raw TDT P-value = 0.306, Adaptive permutation corrected P-value = 0.813	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs7987770	DAOA DAOA-AS1	G/A	TDT: Raw TDT P-value = 0.484, Adaptive permutation corrected P-value = 0.688	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs7986339	DAOA DAOA-AS1	A/G	TDT: Raw TDT P-value = 0.719, Adaptive permutation corrected P-value = 0.438	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs72661139	DAOA DAOA-AS1	T/A	TDT: Raw TDT P-value = 0.572, Adaptive permutation corrected P-value = 0.813	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs72661140	DAOA DAOA-AS1	C/T	TDT: Raw TDT P-value = 0.572, Adaptive permutation corrected P-value = 0.813	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs778293	DAOA	G/A	TDT: Raw TDT P-value = 0.825, Adaptive permutation corrected P-value = 0.688	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs778294	DAOA DAOA-AS1	A/G	TDT: Raw TDT P-value = 0.134, Adaptive permutation corrected P-value = 0.258 STEPC: sib_tdt P-value = 0.017, TG P-value = 0.023	No significant allelic association with BP was found, but as...... No significant allelic association with BP was found, but association underlies the previously observed linkage signals in the CNGsample set was found. More...	Positive
rs778326	DAOA-AS1 DAOA	A/T	TDT: Raw TDT P-value = 0.088, Adaptive permutation corrected P-value = 0.268 STEPC: sib_tdt P-value = 0.026, TG P-value = 0.023	No significant allelic association with BP was found, but as...... No significant allelic association with BP was found, but association underlies the previously observed linkage signals in the CNGsample set was found. More...	Positive
rs778334	DAOA-AS1 DAOA	T/C	TDT: Raw TDT P-value = 1, Adaptive permutation corrected P-value = 0.25	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs778336	DAOA-AS1 DAOA	C/T	TDT: Raw TDT P-value = 0.449, Adaptive permutation corrected P-value = 0.625	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs7981258	DAOA	A/T	TDT: Raw TDT P-value = 0.759, Adaptive permutation corrected P-value = 0.625	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs3916964	DAOA	A/G	TDT: Raw TDT P-value = 0.192, Adaptive permutation corrected P-value = 0.625	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs3916965	DAOA	A/G	TDT: Raw TDT P-value = 0.14, Adaptive permutation corrected P-value = 1	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs3916966	DAOA-AS1 DAOA	G/T	TDT: Raw TDT P-value = 0.162, Adaptive permutation corrected P-value = 0.875	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs3918342	DAOA	C/T	TDT: Raw TDT P-value = 0.942, Adaptive permutation corrected P-value = 0.258	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs41274240	DAOA DAOA-AS1	C/G	TDT: Raw TDT P-value = 0.475, Adaptive permutation corrected P-value = 0.688	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs67705083	DAOA DAOA-AS1	C/A	TDT: Raw TDT P-value = 0.165, Adaptive permutation corrected P-value = 0.381	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs701567	DAOA DAOA-AS1	T/C	TDT: Raw TDT P-value = 0.889, Adaptive permutation corrected P-value = 0.75	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs72661138	DAOA DAOA-AS1	A/G	TDT: Raw TDT P-value = 0.622, Adaptive permutation corrected P-value = 1	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs1815686	DAOA-AS1 DAOA	C/G	STEPC: sib_tdt P-value = 0.039, TG P-value = 0.03	Association underlies the previously observed linkage signal...... Association underlies the previously observed linkage signals in the CNGsample set was found. More...	Positive
rs1421292	DAOA	A/T	TDT: Raw TDT P-value = 0.942, Adaptive permutation corrected P-value = 0.429	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs1935058	DAOA-AS1 DAOA	C/T	TDT: Raw TDT P-value = 0.171, Adaptive permutation corrected P-value = 1 STEPC: sib_tdt P-value = 0.0009, TG P-value = 0.055	No significant allelic association with BP was found, but as...... No significant allelic association with BP was found, but association underlies the previously observed linkage signals in the CNGsample set was found. More...	Positive
rs1935057	DAOA-AS1 DAOA	G/A	TDT: Raw TDT P-value = 0.192, Adaptive permutation corrected P-value = 0.75	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs2012887	DAOA	C/T	TDT: Raw TDT P-value = 0.829, Adaptive permutation corrected P-value = 0.308	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs1935062	DAOA DAOA-AS1	A/C	TDT: Raw TDT P-value = 0.448, Adaptive permutation corrected P-value = 0.813 STEPC: sib_tdt P-value = 0.039, TG P-value = 0.03	No significant allelic association with BP was found, but as...... No significant allelic association with BP was found, but association underlies the previously observed linkage signals in the CNGsample set was found. More...	Positive
rs2391191	DAOA DAOA-AS1	A/G	TDT: Raw TDT P-value = 0.111, Adaptive permutation corrected P-value = 0.875	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs2025522	DAOA	A/G	TDT: Raw TDT P-value = 0.872, Adaptive permutation corrected P-value = 0.688	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs1253464	DAOA	A/G	TDT: Raw TDT P-value = 0.015, Adaptive permutation corrected P-value = 0.563	No significant allelic association with BP was found No significant allelic association with BP was found	Negative
rs1341402	DAOA DAOA-AS1	T/C	TDT: Raw TDT P-value = 0.26, Adaptive permutation corrected P-value = 0.563 STEPC: sib_tdt P-value = 0.0083, TG P-value = 0.038	No significant allelic association with BP was found, but as...... No significant allelic association with BP was found, but association underlies the previously observed linkage signals in the CNGsample set was found. More...	Positive
rs12862108	DAOA DAOA-AS1	G/T	STEPC: sib_tdt P-value = 0.02, TG P-value = 0.024; TDT: Raw TDT P-value = 0.052, Adaptive permutation corrected P-value = 0.293	Association underlies the previously observed linkage signal...... Association underlies the previously observed linkage signals in the CNGsample set was found. More...	Positive

Genes reported by this study for BD (count: 1)