Genetic Determinants of Depression

Dunn, Erin C.; Brown, Ruth C.; Dai, Yael G.; Rosand, Jonathan; Nugent, Nicole R.; Amstadter, Ananda B.; Smoller, Jordan W.

doi:10.1097/hrp.0000000000000054

Cited by 135 publications

(63 citation statements)

References 166 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, to our knowledge, this was the first genome-wide G×E analysis of depression. Prior G×E studies have focused on a relatively limited set of candidate gene polymorphisms, many of which have showed mixed results 10,68 . Second, our study was also the largest GWAS of depressive symptoms conducted specifically in African Americans and Hispanics/Latinas.…”

Section: Discussionmentioning

confidence: 99%

“…For example, simulations studies demonstrate that for common phenotypes (i.e., with prevalence greater than 10%), the quantitative trait approach may have power advantages under certain conditions in population-based samples 9 . GWAS have also neglected the role of gene-environment interaction (G×E) 10 , which many believe contributes to the etiology of depression 11,12 . Previous G×E studies have been limited to candidate genes; these results have been highly controversial 13–16 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genome-Wide Association Study (Gwas) and Genome-Wide by Environment Interaction Study (Gweis) of Depressive Symptoms in African American and Hispanic/Latina Women

et al. 2016

Self Cite

View full text Add to dashboard Cite

Background Genome-wide association studies (GWAS) have been unable to identify variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (G×E) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide environment interaction study (GWEIS) of depressive symptoms. Methods Using data from the SHARe cohort of the Women’s Health Initiative, comprising African Americans (n=7179) and Hispanics/Latinas (n=3138), we examined genetic main effects and G×E with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts. Results No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20kb from GPR139, p=5.75×10−8) and rs75407252 (intronic to CACNA2D3, p=6.99×10−7). In Hispanics/Latinas, the top signals were rs2532087 (located 27kb from CD38, p=2.44×10−7) and rs4542757 (intronic to DCC, p=7.31×10−7). In the GWEIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; p=4.10×10−10; located 14kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG=0.95), suggesting that common variation underlying depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample. Conclusions Our results underscore the need for larger samples, more GWEIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study (Gwas) and Genome-Wide by Environment Interaction Study (Gweis) of Depressive Symptoms in African American and Hispanic/Latina Women

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Complex psychiatric disorders, including mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD), have been shown to run in families and present considerable heritability (Dunn et al, 2015; Kerner, 2015). This is based on observations that first-degree relatives of patients with mood disorders have a higher risk to develop psychiatric disorders than the general population (Potash and DePaulo, 2000; Sullivan et al, 2000), and that monozygotic twins have higher concordance rates than dizygotic twins for these phenotypes (Rice et al, 2002; Smoller and Finn, 2003).…”

Section: Introductionmentioning

confidence: 99%

The role of DNA methylation in the pathophysiology and treatment of bipolar disorder

Fries

McAlpin

et al. 2016

Neuroscience & Biobehavioral Reviews

View full text Add to dashboard Cite

Bipolar disorder (BD) is a multifactorial illness thought to result from an interaction between genetic susceptibility and environmental stimuli. Epigenetic mechanisms, including DNA methylation, can modulate gene expression in response to the environment, and therefore might account for part of the heritability reported for BD. This paper aims to review evidence of the potential role of DNA methylation in the pathophysiology and treatment of BD. In summary, several studies suggest that alterations in DNA methylation may play an important role in the dysregulation of gene expression in BD, and some actually suggest their potential use as biomarkers to improve diagnosis, prognosis, and assessment of response to treatment. This is also supported by reports of alterations in the levels of DNA methyltransferases in patients and in the mechanism of action of classical mood stabilizers. In this sense, targeting specific alterations in DNA methylation represents exciting new treatment possibilities for BD, and the ‘plastic’ characteristic of DNA methylation accounts for a promising possibility of restoring environment-induced modifications in patients.

show abstract

“…Perhaps as a result of low power, many prior studies have not found replicable associations between MDD and candidate genes (Dunn et al, 2015). Identifying candidate genes that interact with the environment to increase risk for MDD has also been plagued by relatively inconsistent patterns of replication (e.g.…”

Section: Introductionmentioning

confidence: 99%

Additive genetic contribution to symptom dimensions in major depressive disorder.

Pearson¹,

Palmer²,

Brick³

et al. 2016

Journal of Abnormal Psychology

View full text Add to dashboard Cite

Major Depressive Disorder is a phenotypically heterogeneous disorder with a complex genetic architecture. In this study, genomic-relatedness-matrix restricted maximum likelihood analysis (GREML) was used to investigate the extent to which variance in depression symptoms/symptom dimensions can be explained by variation in common single nucleotide polymorphisms (SNPs) in a sample of individuals with Major Depressive Disorder (N=1558) who participated in the NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. A principal components analysis of items from the Hamilton Rating Scale for Depression (HRSD) obtained prior to treatment revealed four depression symptom components: 1) appetite, 2) core depression symptoms (e.g., depressed mood, anhedonia), 3) insomnia, and 4) anxiety. These symptom dimensions were associated with SNP-based heritability (h2SNP ) estimates of 30%, 14%, 30% and 5%, respectively. Results indicated that the genetic contribution of common SNPs to depression symptom dimensions were not uniform. Appetite and insomnia symptoms in MDD had a relatively strong genetic contribution whereas the genetic contribution was relatively small for core depression and anxiety symptoms. While in need of replication, these results suggest that future gene discovery efforts may strongly benefit from parsing depression into its constituent parts.

show abstract

Genetic Determinants of Depression

Cited by 135 publications

References 166 publications

Genome-Wide Association Study (Gwas) and Genome-Wide by Environment Interaction Study (Gweis) of Depressive Symptoms in African American and Hispanic/Latina Women

Genome-Wide Association Study (Gwas) and Genome-Wide by Environment Interaction Study (Gweis) of Depressive Symptoms in African American and Hispanic/Latina Women

The role of DNA methylation in the pathophysiology and treatment of bipolar disorder

Additive genetic contribution to symptom dimensions in major depressive disorder.

Contact Info

Product

Resources

About