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

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

doi:10.1038/s41591-023-02352-1

reviewNature MedicineJul 1, 2023GOLD OA

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

TDThomas D. Als MKMitja Kurki JGJakob Grove GVGeorgios Voloudakis KTKaren Therrien

Aarhus University · Lundbeck Foundation · +27 more institutions

PubMed

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Abstract

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…

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298

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FWCI: 86.91
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43

Topics & keywords

Topics

Keywords

Depression (economics)
Pathophysiology
Psychiatry
Medicine
Comorbidity
Major depressive disorder
Bioinformatics
Internal medicine

UN Sustainable Development Goals

Good health and well-being

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