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Genome-wide significant association between a 'negative mood delusions' dimension in bipolar disorder and genetic variation on chromosome 3q26.1.

ABSTRACT: Research suggests that clinical symptom dimensions may be more useful in delineating the genetics of bipolar disorder (BD) than standard diagnostic models. To date, no study has applied this concept to data from genome-wide association studies (GWAS). We performed a GWAS of factor dimensions in 927 clinically well-characterized BD patients of German ancestry. Rs9875793, which is located in an intergenic region of 3q26.1 and in the vicinity of the solute carrier family 2 (facilitated glucose transporter), member 2 gene (SLC2A2), was significantly associated with the factor analysis-derived dimension 'negative mood delusions' (n=927; P=4.65 × 10(-8), odds ratio (OR)=2.66). This dimension was comprised of the symptoms delusions of poverty, delusions of guilt and nihilistic delusions. In case-control analyses, significant association with the G allele of rs9875793 was only observed in the subgroup of BD patients who displayed symptoms of 'negative mood delusions' (allelic ?(2) model: P(G)=0.0001, OR=1.92; item present, n=89). Further support for the hypothesis that rs9875793 is associated with BD in patients displaying 'negative mood delusions' symptom, such as delusions of guilt, was obtained from an European American sample (GAIN/TGEN), which included 1247 BD patients and 1434 controls (P(EA)=0.028, OR=1.27).

SUBMITTER: Meier S

PROVIDER: S-EPMC3565205 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genome-wide significant association between a 'negative mood delusions' dimension in bipolar disorder and genetic variation on chromosome 3q26.1.

Meier S S Mattheisen M M Vassos E E Strohmaier J J Treutlein J J Josef F F Breuer R R Degenhardt F F Mühleisen T W TW Müller-Myhsok B B Steffens M M Schmael C C McMahon F J FJ Nöthen M M MM Cichon S S Schulze T G TG Rietschel M M Kelsoe John R JR Greenwood Tiffany A TA Nievergelt Caroline M CM Barrett Thomas B TB McKinney Rebecca R Shilling Paul D PD Schork Nicholas J NJ Smith Erin N EN Bloss Cinnamon S CS Nurnberger John J Edenberg Howard J HJ Foroud Tatiana T Koller Daniel L DL Gershon Elliot S ES Liu Chun-Yu CY Badner Judith A JA Scheftner William W Lawson William B WB Nwulia Evaristus A EA Hipolito Maria M Coryell William W Rice John J Byerley William W McMahon Francis F Chen David T W DT Schulze Thomas G TG Berrettini Wade W Potash James B JB Zandi Peter P PP Mahon Pamela B PB McInnis Melvin M Craig David D Szelinger Szabolcs S

Translational psychiatry 20120925

Research suggests that clinical symptom dimensions may be more useful in delineating the genetics of bipolar disorder (BD) than standard diagnostic models. To date, no study has applied this concept to data from genome-wide association studies (GWAS). We performed a GWAS of factor dimensions in 927 clinically well-characterized BD patients of German ancestry. Rs9875793, which is located in an intergenic region of 3q26.1 and in the vicinity of the solute carrier family 2 (facilitated glucose tran ...[more]

PMID: 23010768

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Project description:ObjectiveThe Course and Outcome of Bipolar Youth study found that children and adolescents with bipolar spectrum disorders followed 1 of 4 distinct mood trajectories over 8 years of follow-up, with as many as 25% of participants showing a predominantly euthymic course. We evaluated whether similar patterns of illness course are observed in adolescents with bipolar I and II disorder who participated in a 2-year clinical trial.MethodA total of 144 adolescents with bipolar I or II disorder, identified shortly after a mood episode, were assessed over a 2-year period. Participants were randomly assigned to one of 2 psychosocial family treatments during the first 9 months of the study, and pharmacotherapy was provided throughout the 2 years. Using latent class growth analyses, we classified participants into distinct courses of illness based on mood ratings collected over the 2 years. We examined demographic and illness variables as predictors of these course classifications.ResultsLatent class growth analyses indicated four mood trajectories: "predominantly euthymic" (29.9% of sample), "ill with significantly improving course" (11.1%), "moderately euthymic" (26.4%), and "ill with moderately improving course" (32.6%). Adolescents in these classes were euthymic 77.7%, 53.6%, 44.1%, and 18.6% of the weeks of follow-up, respectively. Psychosocial treatment condition and baseline medication exposure were not associated with trajectories. However, youth with more severe baseline depressive symptoms, suicidality, lower quality of life scores, and minority race/ethnicity had more symptomatic courses of illness over time.ConclusionA substantial proportion (25%-30%) of youth with bipolar I or II disorder maintain euthymic states over extended periods of follow-up. Identifying youth who are more and less likely to remain stable over time may help guide psychosocial and pharmacological treatments after an illness episode.Clinical trial registration informationEffectiveness of Family-Focused Treatment Plus Pharmacotherapy for Bipolar Disorder in Adolescents; https://clinicaltrials.gov/; NCT00332098.

Dataset Information

Genome-wide significant association between a 'negative mood delusions' dimension in bipolar disorder and genetic variation on chromosome 3q26.1.

Publications

Genome-wide significant association between a 'negative mood delusions' dimension in bipolar disorder and genetic variation on chromosome 3q26.1.

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