Identification of 15 genetic loci associated with risk of major depression in individuals of European descent.
paper
Cited
Public
- Authors
- Hyde, Craig L; Nagle, Michael W; Tian, Chao; Chen, Xing; Paciga, Sara A; Wendland, Jens R; Tung, Joyce Y; Hinds, David A; Perlis, Roy H; Winslow, Ashley R
- Year
- 2016
- Journal
- Nature genetics
- PMID
- 27479909
- DOI
- 10.1038/ng.3623
- PMCID
- PMC5706769
Despite strong evidence supporting the heritability of major depressive disorder (MDD), previous genome-wide studies were unable to identify risk loci among individuals of European descent. We used self-report data from 75,607 individuals reporting clinical diagnosis of depression and 231,747 individuals reporting no history of depression through 23andMe and carried out meta-analysis of these results with published MDD genome-wide association study results. We identified five independent variants from four regions associated with self-report of clinical diagnosis or treatment for depression. Loci with a P value <1.0 Γ 10(-5) in the meta-analysis were further analyzed in a replication data set (45,773 cases and 106,354 controls) from 23andMe. A total of 17 independent SNPs from 15 regions reached genome-wide significance after joint analysis over all three data sets. Some of these loci were also implicated in genome-wide association studies of related psychiatric traits. These studies provide evidence for large-scale consumer genomic data as a powerful and efficient complement to data collected from traditional means of ascertainment for neuropsychiatric disease genomics.
Discovery phase meta-analysis of 23andMe self-report ascertainment of major depression (75,607 cases and 231,747 controls) and PGC MDD (9,240 cases and 9,519 controls). a) Manhattan plot of Discovery phase 23andMe GWAS. LD score regression calculated intercept was used for inflation correction. The threshold for genome-wide significance (p < 5Γ10β8) is indicated by the purple line. Red dots represent SNPs with p-values smaller than the genome-wide significant threshold. Regions labeled in black denote loci that reached genome-wide significance in the join-analysis. b) Q-Q plot for the 23andMe MDD GWAS.
Regional association plots for genome-wide significant regions and secondary independent signals identified in each region. a) OLFM4 locus (rs12552), b) TMEM161B-MEF2C (rs10514299), c) MEIS2-TMCO5A locus (rs8025231), and d) NEGR1 locus (rs11209948). Secondary signals in TMEM161B-MEF2C and NEGR1 (rs454214, rs2422321 respectively) are shown. Purple diamonds represent smallest p-value for each locus.
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| Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients. | Karis K et al. | β | 2018 | β |
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| Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes. | Aponte JL et al. | β | 2018 | β |
| Co-expression network analysis of peripheral blood transcriptome identifies dysregulated protein processing in endoplasmic reticulum and immune response in recurrent MDD in older adults. | Ciobanu LG et al. | β | 2018 | β |
| Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. | Culverhouse RC et al. | β | 2018 | β |
| Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder. | Li X et al. | β | 2018 | β |
| Comparison of methods that use whole genome data to estimate the heritability and genetic architecture of complex traits. | Evans LM et al. | β | 2018 | β |
| Convergence of evidence from a methylome-wide CpG-SNP association study and GWAS of major depressive disorder. | Aberg KA et al. | β | 2018 | β |
| Cross-species evidence from human and rat brain transcriptome for growth factor signaling pathway dysregulation in major depression. | Carboni L et al. | β | 2018 | β |
| DNA methylation and clinical response to antidepressant medication in major depressive disorder: A review and recommendations. | Lisoway AJ et al. | β | 2018 | β |
| DNA sequence-level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders. | Ryan NM et al. | β | 2018 | β |
| Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium. | Peyrot WJ et al. | β | 2018 | β |
| Elucidating the genetic basis of social interaction and isolation. | Day FR et al. | β | 2018 | β |
| Finding associated variants in genome-wide association studies on multiple traits. | Gai L et al. | β | 2018 | β |
| FoxO1, A2M, and TGF-Ξ²1: three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses. | Cattaneo A et al. | β | 2018 | β |
| From the Psychiatrist's Couch to Induced Pluripotent Stem Cells: Bipolar Disease in a Dish. | Hoffmann A et al. | β | 2018 | β |
| Genetic nature or genetic nurture? Introducing social genetic parameters to quantify bias in polygenic score analyses. | Trejo S et al. | β | 2018 | β |
| Genetics Factors in Major Depression Disease. | Shadrina M et al. | β | 2018 | β |
| Genetics of biologically based psychological differences. | Sallis H et al. | β | 2018 | β |
| Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program. | Klarin D et al. | β | 2018 | β |
| Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. | Wray NR et al. | β | 2018 | β |
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| Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. | Zhou H et al. | β | 2018 | β |
| Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry. | Sanchez-Roige S et al. | β | 2018 | β |
| Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. | Howard DM et al. | β | 2018 | β |
| Genome-wide association study of depressive symptoms in the Hispanic Community Health Study/Study of Latinos. | Dunn EC et al. | β | 2018 | β |
| Genome-wide gene-environment interaction in depression: A systematic evaluation of candidate genes: The childhood trauma working-group of PGC-MDD. | Van der Auwera S et al. | β | 2018 | β |
| Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder. | Arnau-Soler A et al. | β | 2018 | β |
| Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank. | Hall LS et al. | β | 2018 | β |
| Genome-wide scan of depressive symptomatology in two representative cohorts in the United States and the United Kingdom. | Mekli K et al. | β | 2018 | β |
| Genomic Approaches to Posttraumatic Stress Disorder: The Psychiatric Genomic Consortium Initiative. | Nievergelt CM et al. | β | 2018 | β |
| Heterogeneous stock rats: a model to study the genetics of despair-like behavior in adolescence. | Holl K et al. | β | 2018 | β |
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| Imaging genetics paradigms in depression research: Systematic review and meta-analysis. | Pereira LP et al. | β | 2018 | β |
| Importance of the brain corticosteroid receptor balance in metaplasticity, cognitive performance and neuro-inflammation. | de Kloet ER et al. | β | 2018 | β |
| International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets. | Caraci F et al. | β | 2018 | β |
| Investigating the genetic architecture of general and specific psychopathology in adolescence. | Jones HJ et al. | β | 2018 | β |
| Investigation of serum levels of sortilin in response to antidepressant treatment. | ButtenschΓΈn HN et al. | β | 2018 | β |
| Is familial risk for depression confounded by individual and familial socioeconomic factors and neighborhood environmental factors? A 7-year follow-up study in Sweden. | Hamano T et al. | β | 2018 | β |
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| Molecular and Functional Sex Differences of Noradrenergic Neurons in the Mouse Locus Coeruleus. | Mulvey B et al. | β | 2018 | β |
| Molecular Genetic Analysis Subdivided by Adversity Exposure Suggests Etiologic Heterogeneity in Major Depression. | Peterson RE et al. | β | 2018 | β |
| Molecular genetic overlap between migraine and major depressive disorder. | Yang Y et al. | β | 2018 | β |
| Multi-trait analysis of genome-wide association summary statistics using MTAG. | Turley P et al. | β | 2018 | β |
| Neuronal Growth and Behavioral Alterations in Mice Deficient for the Psychiatric Disease-Associated <i>Negr1</i> Gene. | Singh K et al. | β | 2018 | β |
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| Novel functional variants at the GWAS-implicated loci might confer risk to major depressive disorder, bipolar affective disorder and schizophrenia. | Bryzgalov LO et al. | β | 2018 | β |
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