An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

作者：Direk Nese; Williams Stephanie; Smith Jennifer A; Ripke Stephan; Air Tracy; Amare Azmeraw T; Amin Najaf; Baune Bernhard T; Bennett David A; Blackwood Douglas H R; Boomsma Dorret; Breen Gerome; Buttenschon Henriette N; Byrne Enda M; Borglum Anders D; Castelao Enrique; Cichon Sven; Clarke Toni Kim; Cornelis Marilyn C; Dannlowski Udo; De Jager Philip L; Demirkan Ayse; Domenici Enrico; van Duijn Cornelia M; Dunn Erin C; Eriksson Johan G; Esko Tonu

来源：Biological Psychiatry, 2017, 82(5): 322-329.

DOI：10.1016/j.biopsych.2016.11.013

• CHARGE consortium
• Depressive symptoms
• FHIT gene
• Genome-wide association study
• Major depressive disorder
• Psychiatric Genomics Consortium

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 x 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 x 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.

• 出版日期2017-9-1
• 单位MIT; NIH; 上海市精神卫生中心; 西北大学