TY - JOUR
T1 - Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways
AU - Howard, David M.
AU - Adams, Mark J.
AU - Shirali, Masoud
AU - Clarke, Toni-Kim
AU - Marioni, Riccardo E.
AU - Davies, Gail
AU - Coleman, Jonathan R. I.
AU - Alloza, Clara
AU - Shen, Xueyi
AU - Barbu, Miruna C.
AU - Wigmore, Eleanor M.
AU - Gibson, Jude
AU - Hagenaars, Saskia P.
AU - Lewis, Cathryn M.
AU - Ward, Joey
AU - Smith, Daniel J.
AU - Sullivan, Patrick F.
AU - Haley, Chris S.
AU - Breen, Gerome
AU - Deary, Ian J.
AU - McIntosh, Andrew M.
PY - 2018/4/16
Y1 - 2018/4/16
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-018-03819-3
DO - 10.1038/s41467-018-03819-3
M3 - Article
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1470
ER -