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The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach.

ABSTRACT: BACKGROUND: The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies. METHODS: In a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188) we examined seven single nucleotide polymorphisms (SNPs) around DAOA/G30 (rs3916966, rs1935058, rs2391191, rs1935062, rs947267, rs3918342, and rs9558575) for genetic association in a polydiagnostic approach (ICD 10; Leonhard's classification). RESULTS: No single marker showed evidence of overall association with affective disorder neither in ICD10 nor Leonhard's classification. Haplotype analysis revealed no association with recurrent unipolar depression or bipolar disorder according to ICD10, within Leonhard's classification manic-depression was associated with a 3-locus haplotype (rs2391191, rs1935062, and rs3916966; P = 0.022) and monopolar depression with a 5-locus combination at the DAOA/G30 core region (P = 0.036). CONCLUSION: Our data revealed potential evidence for partially overlapping risk haplotypes at the DAOA/G30 locus in Leonhard's affective psychoses, but do not support a common genetic contribution of the DAOA/G30 gene complex to the pathogenesis of affective disorders.

SUBMITTER: Gawlik M

PROVIDER: S-EPMC2921107 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach.

Gawlik Micha M Wehner Ingeborg I Mende Meinhard M Jung Sven S Pfuhlmann Bruno B Knapp Michael M Stöber Gerald G

BMC psychiatry 20100729

<h4>Background</h4>The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies.<h4>Methods</h4>In a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188) we examined seven single nucleotide polymorphisms (SNPs) around DAOA/G30 (rs3916966, rs1935058, rs23911 ...[more]

PMID: 20667145

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Project description:BackgroundHaplotype-based approaches have been extensively studied for case-control association mapping in recent years. It has been shown that haplotype methods can provide more consistent results comparing to single-locus based approaches, especially in cases where causal variants are not typed. Improved power has been observed by clustering similar or rare haplotypes into groups to reduce the degrees of freedom of association tests. For family-based association studies, one commonly used strategy is Transmission Disequilibrium Tests (TDT), which examine the imbalanced transmission of alleles/haplotypes to affected and normal children. Many extensions have been developed to deal with general pedigrees and continuous traits.ResultsIn this paper, we propose a new haplotype-based association method for family data that is different from the TDT framework. Our approach (termed F_HapMiner) is based on our previous successful experiences on haplotype inference from pedigree data and haplotype-based association mapping. It first infers diplotype pairs of each individual in each pedigree assuming no recombination within a family. A phenotype score is then defined for each founder haplotype. Finally, F_HapMiner applies a clustering algorithm on those founder haplotypes based on their similarities and identifies haplotype clusters that show significant associations with diseases/traits. We have performed extensive simulations based on realistic assumptions to evaluate the effectiveness of the proposed approach by considering different factors such as allele frequency, linkage disequilibrium (LD) structure, disease model and sample size. Comparisons with single-locus and haplotype-based TDT methods demonstrate that our approach consistently outperforms the TDT-based approaches regardless of disease models, local LD structures or allele/haplotype frequencies.ConclusionWe present a novel haplotype-based association approach using family data. Experiment results demonstrate that it achieves significantly higher power than TDT-based approaches.

Project description:OBJECTIVE:Isotretinoin (13-cis-retinoic acid), approved by the US Food and Drug Administration for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psychosis. Retinoic acid, the active form of vitamin A, regulates gene expression in the brain, and isotretinoin is its 13-cis isomer. Retinoids represent a group of compounds derived from vitamin A that perform a large variety of functions in many systems, in particular the central nervous system, and abnormal retinoid levels can have neurologic effects. Although infrequent, proper recognition and treatment of psychiatric side effects in acne patients is critical given the risk of death and disability. This article reviews the evidence for isotretinoin's relationships with depression and suicidality. DATA SOURCES:The PsycINFO, MEDLINE, and PubMed searchable database indexes were searched for articles published in the English language from 1960 to June 2010 using the key words isotretinoin, retinoids, retinoic acid, depression, depressive disorders, and vitamin A. Evidence examined includes (1) case reports; (2) temporal association between onset of depression and exposure to the drug; (3) challenge-rechallenge cases; (4) class effect (other compounds in the same class, like vitamin A, having similar neuropsychiatric effects); (5) dose response; and (6) biologically plausible mechanisms. STUDY SELECTION:All articles in the literature related to isotretinoin, depression, and suicide were reviewed, as well as articles related to class effect, dose response, and biologic plausibility. DATA EXTRACTION:Information from individual articles in the literature was extracted, including number of episodes of depression, suicidality, suicide, psychosis, violence and aggression, past psychiatric history, time of onset in relation to isotretinoin usage, medication dosage, duration of treatment, and dechallenge and challenge history. RESULTS:The literature reviewed is consistent with associations of isotretinoin administration with depression and with suicide in a subgroup of vulnerable individuals. CONCLUSIONS:The relationship between isotretinoin and depression may have implications for a greater understanding of the neurobiology of affective disorders.

Project description:ImportancePatients with idiopathic sudden sensorineural hearing loss (ISSNHL) often experience permanent hearing impairment, which could result in psychological perturbations. However, the relationship between ISSNHL and affective disorders, including depression, anxiety, and bipolar disorder, has not been fully evaluated.ObjectiveTo investigate the potential relationship between ISSNHL and affective disorders using nationwide representative cohort sample data.Design, setting, and participantsThis study used a nationwide propensity score-matched cohort sample from the Korean National Health Insurance Service database from 2002 through 2013, which comprises data from approximately 1 million patients. The study included 1425 patients with ISSNHL and 7125 individuals without ISSNHL who were matched using propensity score matching, according to sociodemographic factors and enrollment year.Main outcomes and measuresSurvival analysis, the log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of developing affective disorders (anxiety, depression, and bipolar disorder) for each group.ResultsOf the total study population of 8550 (51.5% female), 961 developed affective disorders during the 11-year follow-up: 225 in the ISSNHL group (15.8%) and 736 in the comparison group (10.3%). We examined a total of 96 885.5 person-years (81 177.4 person-years in the comparison group and 15 708.1 person-years in the ISSNHL group). The incidence of affective disorders was 14.3 per 1000 person-years in the ISSNHL group and 9.1 per 1000 person-years in the comparison group. After adjustment for other factors, individuals with ISSNHL developed affective disorders more frequently than those in the comparison group (HR, 1.50; 95% CI, 1.30-1.75). Among the affective disorders, the HR of developing depression (HR, 1.66; 95% CI, 1.44-1.91) and anxiety disorder (HR, 1.79; 95% CI, 1.56-2.05) but not bipolar disorder (HR, 0.95; 95% CI, 0.54-1.70), was significantly greater in patients with ISSNHL.Conclusions and relevanceThis cohort study suggests that ISSNHL is associated with an increased incidence of affective disorders, specifically depression and anxiety. Therefore, these findings suggest that clinicians should monitor patients with ISSNHL carefully, and take specific precautions to reduce their risk of depression and anxiety disorder.

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The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach.

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The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach.

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