@article{85e4ef0117f8479baccad886aea226a2,
title = "Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies",
abstract = "In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses. The associations are enriched for antidepressant targets and provide potential repurposing opportunities. Polygenic scores trained using European or multi-ancestry data predicted MD status across all ancestries, explaining up to 5.8% of MD liability variance in Europeans. These findings advance our global understanding of MD and reveal biological targets that may be used to target and develop pharmacotherapies addressing the unmet need for effective treatment.",
keywords = "depression, drugs, enrichment, genetic, genome-wide association study, GWAS, neurons, pharmacotherapies, targets",
author = "{Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Adams, {Mark J.} and Fabian Streit and Xiangrui Meng and Swapnil Awasthi and Adey, {Brett N.} and Choi, {Karmel W.} and Chundru, {V. Kartik} and Coleman, {Jonathan R.I.} and Bart Ferwerda and Foo, {Jerome C.} and Gerring, {Zachary F.} and Olga Giannakopoulou and Priya Gupta and Hall, {Alisha S.M.} and Arvid Harder and Howard, {David M.} and Christopher H{\"u}bel and Kwong, {Alex S.F.} and Levey, {Daniel F.} and Mitchell, {Brittany L.} and Guiyan Ni and Ota, {Vanessa K.} and Oliver Pain and Pathak, {Gita A.} and Schulte, {Eva C.} and Xueyi Shen and Thorp, {Jackson G.} and Alicia Walker and Shuyang Yao and Jian Zeng and Johan Zvrskovec and Dag Aarsland and Actkins, {Ky'Era V.} and Mazda Adli and Esben Agerbo and Mareike Aichholzer and Allison Aiello and Air, {Tracy M.} and Als, {Thomas D.} and Evelyn Andersson and Andlauer, {Till F.M.} and Volker Arolt and Helga Ask and Julia B{\"a}ckman and Sunita Badola and Clive Ballard and Karina Banasik and Bass, {Nicholas J.} and Beekman, {Aartjan T.F.} and Stein, {Dan J.}",
note = "Publisher Copyright: {\textcopyright} 2024 The Authors",
year = "2025",
month = feb,
day = "6",
doi = "10.1016/j.cell.2024.12.002",
language = "אנגלית",
volume = "188",
pages = "640--652.e9",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "3",
}