Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 9 (1), 1470

Genome-wide Association Study of Depression Phenotypes in UK Biobank Identifies Variants in Excitatory Synaptic Pathways

Collaborators, Affiliations

Genome-wide Association Study of Depression Phenotypes in UK Biobank Identifies Variants in Excitatory Synaptic Pathways

David M Howard et al. Nat Commun.

Abstract

Depression is a polygenic trait that causes extensive periods of disability. Previous genetic studies have identified common risk variants which have progressively increased in number with increasing sample sizes of the respective studies. Here, we conduct a genome-wide association study in 322,580 UK Biobank participants for three depression-related phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. We identify 17 independent loci that are significantly associated (P < 5 × 10-8) across the three phenotypes. The direction of effect of these loci is consistently replicated in an independent sample, with 14 loci likely representing novel findings. Gene sets are enriched in excitatory neurotransmission, mechanosensory behaviour, post synapse, neuron spine and dendrite functions. Our findings suggest that broad depression is the most tractable UK Biobank phenotype for discovering genes and gene sets that further our understanding of the biological pathways underlying depression.

Conflict of interest statement

I.J.D. is a participant in UK Biobank. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Manhattan plot of the observed –log10 P-values of each variant for an association with broad depression (n = 322,580) in the UK Biobank cohort. Variants are positioned according to the GRCh37 assembly
Fig. 2
Fig. 2
Manhattan plot of the observed –log10 P-values of each variant for an association with probable major depressive disorder (n = 174,519) in the UK Biobank cohort. Variants are positioned according to the GRCh37 assembly
Fig. 3
Fig. 3
Manhattan plot of the observed –log10 P-values of each variant for an association with International Classification of Diseases-coded major depressive disorder (n = 217,584) in the UK Biobank cohort. Variants are positioned according to the GRCh37 assembly
Fig. 4
Fig. 4
Forest plot of the estimated SNP-based heritability of broad depression by recruitment centre and region. Heritabilities are provided where there was power of at least 30% to detect a heritability >0 with a trait heritability of 9%, a type I error of 0.05, a trait prevalence of 0.3527 and a variance of the SNP-derived genetic relationships of 2 × 10−5

Similar articles

See all similar articles

Cited by 36 articles

See all "Cited by" articles

References

    1. World Health Organization. Depression and other common mental disorders. WHO/MSD/MER/2017.2, 1-24 (WHO, Geneva, 2017).
    1. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am. J. Psychiatry. 2000;157:1552–1562. doi: 10.1176/appi.ajp.157.10.1552. - DOI - PubMed
    1. Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium., Wray, N. R. & Sullivan, P. F. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Preprint at bioRxiv 10.1101/167577 (2017). - PMC - PubMed
    1. Hyde CL, et al. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat. Genet. 2016;48:1031–1036. doi: 10.1038/ng.3623. - DOI - PMC - PubMed
    1. Okbay A, et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat. Genet. 2016;48:624–633. doi: 10.1038/ng.3552. - DOI - PMC - PubMed

Publication types

MeSH terms

Feedback