Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

By David Mark Howard, M. Adams, Toni‐Kim Clarke, J. Hafferty, J. Gibson, M. Shirali, J. Coleman, S. Hagenaars, J. Ward, E. Wigmore and 28 more. Nature Neuroscience, 2019

2,238 citations recorded by the source corpus.

Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches. The authors conducted a genetic meta-analysis of depression and found 269 associated genes. These genes highlight several potential drug repositioning opportunities, and relationships with depression were found for neuroticism and smoking.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4577583573d02a179e1e2779ffe112fe516f64f5

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

The genetic architecture of the human cerebral cortex (2020, background): “56), depressive symptoms (57), major depressive disorder (58), and neuroticism (29) (Fig.”
An integrated framework for local genetic correlation analysis (2022, background): “…behavioral phenotypes was locus 1,719 (chr11:112,755,447–113,889,019; Supplementary Table 27; for depression, neuroticism, educational attainment, alcohol intake, WHR and BMI), which contained NCAM1 and DRD2 , which have been frequently implicated in behavioral and psychiatric phenotypes 2,31–36 .”