Dataset Information

Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders.

ABSTRACT: Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders.

SUBMITTER: Xiao X

PROVIDER: S-EPMC5802692 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders.

Xiao Xiao X Wang Lu L Wang Chuang C Yuan Ti-Fei TF Zhou Dongsheng D Zheng Fanfan F Li Lingyi L Grigoroiu-Serbanescu Maria M Ikeda Masashi M Iwata Nakao N Takahashi Atsushi A Kamatani Yoichiro Y Kubo Michiaki M Preisig Martin M Kutalik Zoltán Z Castelao Enrique E Pistis Giorgio G Amin Najaf N van Duijn Cornelia M CM Forstner Andreas J AJ Strohmaier Jana J Hecker Julian J Schulze Thomas G TG Müller-Myhsok Bertram B Reif Andreas A Mitchell Philip B PB Martin Nicholas G NG Schofield Peter R PR Cichon Sven S Nöthen Markus M MM Chang Hong H Luo Xiong-Jian XJ Fang Yiru Y Yao Yong-Gang YG Zhang Chen C Rietschel Marcella M Li Ming M

Translational psychiatry 20171211 12

Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately all ...[more]

PMID: 29225345

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Project description:OBJECTIVES:Mood instability is a clinically important phenomenon but has received relatively little research attention. The objective of this study was to assess the impact of mood instability on clinical outcomes in a large sample of people receiving secondary mental healthcare. DESIGN:Observational study using an anonymised electronic health record case register. SETTING:South London and Maudsley NHS Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. PARTICIPANTS:27,704 adults presenting to SLaM between April 2006 and March 2013 with a psychotic, affective or personality disorder. EXPOSURE:The presence of mood instability within 1 month of presentation, identified using natural language processing (NLP). MAIN OUTCOME MEASURES:The number of days spent in hospital, frequency of hospital admission, compulsory hospital admission and prescription of antipsychotics or non-antipsychotic mood stabilisers over a 5-year follow-up period. RESULTS:Mood instability was documented in 12.1% of people presenting to mental healthcare services. It was most frequently documented in people with bipolar disorder (22.6%), but was common in people with personality disorder (17.8%) and schizophrenia (15.5%). It was associated with a greater number of days spent in hospital (β coefficient 18.5, 95% CI 12.1 to 24.8), greater frequency of hospitalisation (incidence rate ratio 1.95, 1.75 to 2.17), greater likelihood of compulsory admission (OR 2.73, 2.34 to 3.19) and an increased likelihood of prescription of antipsychotics (2.03, 1.75 to 2.35) or non-antipsychotic mood stabilisers (2.07, 1.77 to 2.41). CONCLUSIONS:Mood instability occurs in a wide range of mental disorders and is not limited to affective disorders. It is generally associated with relatively poor clinical outcomes. These findings suggest that clinicians should screen for mood instability across all common mental health disorders. The data also suggest that targeted interventions for mood instability may be useful in patients who do not have a formal affective disorder.

Project description:ImportanceMood disorders are associated with increased body weight, especially in females, but it remains unknown when the weight increase starts.ObjectivesTo examine sex-specific weight trajectories associated with familial mood disorder risk and determine the age at which youth at familial risk for mood disorders begin to diverge in weight from controls.Design, setting, and participantsThis community-based, single-center, acceleration cohort study of youth at familial risk for mood disorders and controls with yearly follow-ups (mean [SD], 5 [2.1] years) from January 1, 2014, to December 31, 2022, assessed 394 unaffected female and male offspring (aged 3 to 20 years) of parents with or without a mood disorder. Parents with mood (depressive or bipolar) disorders were recruited through adult mental health services. Parents of control participants were matched on age and socioeconomic factors and recruited through acquaintance referrals or schools.ExposuresThe youth in the familial mood risk group had at least 1 parent with a major mood disorder, whereas control youth did not have a parent with a mood disorder.Main outcomes and measuresBody mass indexes (BMIs) were calculated as weight in kilograms divided by height in meters squared from measured weight and height at annual assessments and then converted to age- and sex-adjusted z scores (zBMIs). Repeated-measure regressions examined the association between zBMI and age in youth at familial risk of mood disorders and controls while accounting for sex. Sensitivity analyses accounted for socioeconomic status, prematurity, and birth weight.ResultsOf 394 participants (mean [SD] age, 11.5 [3.6] years; 203 [51.5%] female), youths at familial risk for mood disorders showed overall no difference in body weight (β = 0.12; 95% CI, 0.01-0.24) from controls. A sex-specific difference was detected, with females at familial risk showing a rapid peripubertal increase in body weight, leading to significantly increased zBMIs at 12 years and older compared with controls (β = 0.57; 95% CI, 0.31-0.82) independent of socioeconomic status, prematurity, or birth weight. Males did not differ from controls at any age.Conclusions and relevanceIn this cohort study, females with a family history of mood disorders were prone to weight gain starting around puberty and predating mood disorder onset. Early interventions aiming to prevent adverse mental and physical outcomes in this vulnerable group need to start in childhood.

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Dataset Information

Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders.

Publications

Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders.

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