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An analysis of two genome-wide association meta-analyses identifies a new locus for broad depression phenotype.

Biol. Psychiatry 82, 322-329 (2017)
Open Access Green as soon as Postprint is submitted to ZB.
Background: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. Methods: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a . p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. Results: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10-9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10-9). Conclusions: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Charge Consortium ; Depressive Symptoms ; Fhit Gene ; Genome-wide Association Study ; Major Depressive Disorder ; Psychiatric Genomics Consortium; National Comorbidity Survey; Major Depression; Minor Depression; Subthreshold Depression; Symptoms; Risk; Disorder; Stress; Heritability; Population
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