Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses

Thomas D. Als, Mitja Kurki, Jakob Grove, Georgios Voloudakis, Karen Therrien, Elisa Tasanko, Trine Tollerup Nielsen, Joonas Naamanka, Kumar Veerapen, Daniel F. Levey, Jaroslav Bendl, Jonas Bybjerg‐Grauholm, Biao Zeng, Ditte Demontis, Anders Rosengren, Georgios Athanasiadis, Marie Bækved-Hansen, Per Qvist, G. Bragi Walters, Thorgeir E. Thorgeirsson, Hreinn Stefánsson, Katherine L. Musliner, Veera M. Rajagopal, Leila Farajzadeh, Janne Pia Thirstrup, Bjarni J. Vilhjálmsson, John J. McGrath, Manuel Mattheisen, Sandra Meier, Esben Agerbo, Kāri Stefánsson, Merete Nordentoft, Thomas Werge, David M. Hougaard, Preben Bo Mortensen, Murray B. Stein, Joel Gelernter, Iiris Hovatta, Panos Roussos, Mark J. Daly, Ole Mors, Aarno Palotie, Anders D. Børglum

Nature Medicine · 2023

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Summary

Depression is a common psychiatric disorder and a leading cause of disability worldwide. Here we conducted a genome-wide association study meta-analysis of six datasets, including >1.3 million individuals (371,184 with depression) and identified 243 risk loci. Overall, 64 loci were new, including genes encoding glutamate and GABA receptors, which are targets for antidepressant drugs. Intersection with functional genomics data prioritized likely causal genes and revealed new enrichment of prenatal GABAergic neurons, astrocytes and oligodendrocyte lineages. We found depression to be highly polygenic, with ~11,700 variants explaining 90% of the single-nucleotide polymorphism heritability, estimating that >95% of risk variants for other psychiatric disorders (anxiety, schizophrenia, bipolar di

Source type
Peer-reviewed study
DOI
10.1038/s41591-023-02352-1
Catalogue ID
SNmois81sf-l3i9bn
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