Dataset Information

Genetic risk profiles for depression and anxiety in adult and elderly cohorts.

ABSTRACT: The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was defined based on a GWA study of 1738 adult cases and 1802 controls. The genetic risk scores were tested in two population-based samples of elderly participants. The genetic risk profiles were evaluated for depression and anxiety in the Rotterdam Study cohort and the Erasmus Rucphen Family (ERF) study. The genetic risk scores were significantly associated with different measures of depression and explained up to ?0.7% of the variance in depression in Rotterdam Study and up to ?1% in ERF study. The genetic score for depression was also significantly associated with anxiety explaining up to 2.1% in Rotterdam study. These findings suggest the presence of many genetic loci of small effect that influence both depression and anxiety. Remarkably, the predictive value of these profiles was as large in the sample of elderly participants as in the middle-aged samples.

SUBMITTER: Demirkan A

PROVIDER: S-EPMC3142964 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic risk profiles for depression and anxiety in adult and elderly cohorts.

Demirkan A A Penninx B W J H BW Hek K K Wray N R NR Amin N N Aulchenko Y S YS van Dyck R R de Geus E J C EJ Hofman A A Uitterlinden A G AG Hottenga J-J JJ Nolen W A WA Oostra B A BA Sullivan P F PF Willemsen G G Zitman F G FG Tiemeier H H Janssens A C J W AC Boomsma D I DI van Duijn C M CM Middeldorp C M CM

Molecular psychiatry 20100622 7

The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was def ...[more]

PMID: 20567237

Similar Datasets

Project description:ObjectiveDepression has been associated with metabolomic alterations. Depressive and anxiety disorders are often comorbid diagnoses and are suggested to share etiology. We investigated whether differential metabolomic alterations are present between anxiety and depressive disorders and which clinical characteristics of these disorders are related to metabolomic alterations.MethodsData were from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with current comorbid anxiety and depressive disorders (N = 531), only a current depression (N = 304), only a current anxiety disorder (N = 548), remitted depressive and/or anxiety disorders (N = 897), and healthy controls (N = 634). Forty metabolites from a proton nuclear magnetic resonance lipid-based metabolomics panel were analyzed. First, we examined differences in metabolites between disorder groups and healthy controls. Next, we assessed whether depression or anxiety clinical characteristics (severity and symptom duration) were associated with metabolites.ResultsAs compared to healthy controls, seven metabolomic alterations were found in the group with only depression, reflecting an inflammatory (glycoprotein acetyls; Cohen's d = 0.12, p = 0.002) and atherogenic-lipoprotein-related (e.g., apolipoprotein B: Cohen's d = 0.08, p = 0.03, and VLDL cholesterol: Cohen's d = 0.08, p = 0.04) profile. The comorbid group showed an attenuated but similar pattern of deviations. No metabolomic alterations were found in the group with only anxiety disorders. The majority of metabolites associated with depression diagnosis were also associated with depression severity; no associations were found with anxiety severity or disease duration.ConclusionWhile substantial clinical overlap exists between depressive and anxiety disorders, this study suggests that altered inflammatory and atherogenic-lipoprotein-related metabolomic profiles are uniquely associated with depression rather than anxiety disorders.

Project description:Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N = 4,178, 65.5% female; mean age = 41.5 years; N = 1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age = 45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.

Project description:BackgroundEvidence from previous studies has confirmed that functionally impaired elderly individuals are susceptible to comorbid anxiety and depression. Network theory holds that the comorbidity emerges from interactions between anxiety and depression symptoms. This study aimed to investigate the fine-grained relationships among anxiety and depression symptoms in the functionally impaired elderly and identify central and bridge symptoms to provide potential targets for intervention of these two comorbid disorders.MethodsA total of 325 functionally impaired elderly individuals from five communities in Xi'an, China, were recruited for our investigation. The GAD-7 and PHQ-9 were used to measure anxiety and depression, respectively. SPSS 22.0 software was used for descriptive statistics, and R 4.1.1 software was used for network model construction, expected influence (EI) evaluation and bridge expected influence (BEI) evaluation.ResultsIn the network, there were 35 edges (indicating partial correlations between symptoms) across the communities of anxiety and depression, among which the strongest edge was A1 "Nervousness or anxiety"-D2 "Depressed or sad mood." A2 "Uncontrollable worry" and D2 "Depressed or sad mood" had the highest EI values in the network, while A6 "Irritable" and D7 "Concentration difficulties" had the highest BEI values of their respective community. In the flow network, the strongest direct edge of D9 "Thoughts of death" was with D6 "Feeling of worthlessness."ConclusionComplex fine-grained relationships exist between anxiety and depression in functionally impaired elderly individuals. "Uncontrollable worry," "depressed or sad mood," "irritable" and "concentration difficulties" are identified as the potential targets for intervention of anxiety and depression. Our study emphasizes the necessity of suicide prevention for functionally impaired elderly individuals, and the symptom "feeling of worthlessness" can be used as an effective target.

Dataset Information

Genetic risk profiles for depression and anxiety in adult and elderly cohorts.

Publications

Genetic risk profiles for depression and anxiety in adult and elderly cohorts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets