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Scientific paper - Original scientific paper
Identifying the Common Genetic Basis of Antidepressant Response
Biological Psychiatry Global Open Science, 2 (2022), 2; 115-126. https://doi.org/10.1016/j.bpsgos.2021.07.008
(GSRD Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium) Pain, Oliver; Hodgson, Karen; Trubetskoy, Vassily; Ripke, Stephan; Marshe, Victoria S.; Adams, Mark J.; Byrne, Enda M.; Campos, Adrian I.; Carrillo-Roa, Tania; Cattaneo, Annamaria; Als, Thomas D.; Souery, Daniel; Dernovsek, Mojca Z.; Fabbri, Chiara; Hayward, Caroline; Henigsberg, Neven; Hauser, Joanna; Kennedy, James L.; Lenze, Eric J.; Lewis, Glyn; Müller, Daniel J.; Martin, Nicholas G.; Mulsant, Benoit H.; Mors, Ole; Perroud, Nader; Porteous, David J.; Rentería, Miguel E.; Reynolds III, Charles F.; Rietschel, Marcella; Uher, Rudolf; Wigmore, Eleanor M.; Maier, Wolfgang; Wray, Naomi R.; Aitchison, Katherine J.; Arolt, Volker; Baune, Bernhard T.; Biernacka, Joanna M.; Bondolfi, Guido; Domschke, Katharina; Kato, Masaki; Li, Qingqin S.; Liu, Yu-Li; Serretti, Alessandro; Tsai, Shih-Jen; Turecki, Gustavo; Weinshilboum, Richard; McIntosh, Andrew M.; Lewis, Cathryn M. More authors...

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Pain, O., Hodgson, K., Trubetskoy, V., Ripke, S., Marshe, V. S., Adams, M. J. ... Lewis, C. M. (2022). Identifying the Common Genetic Basis of Antidepressant Response. Biological Psychiatry Global Open Science, 2. (2), 115-126. doi: 10.1016/j.bpsgos.2021.07.008

Pain, Oliver, et al. "Identifying the Common Genetic Basis of Antidepressant Response." Biological Psychiatry Global Open Science, vol. 2, no. 2, 2022, pp. 115-126. https://doi.org/10.1016/j.bpsgos.2021.07.008

Pain, Oliver, Karen Hodgson, Vassily Trubetskoy, Stephan Ripke, Victoria S. Marshe, Mark J. Adams, Enda M. Byrne, et al. "Identifying the Common Genetic Basis of Antidepressant Response." Biological Psychiatry Global Open Science 2, no. 2 (2022): 115-126. https://doi.org/10.1016/j.bpsgos.2021.07.008

Pain, O., et al. (2022) 'Identifying the Common Genetic Basis of Antidepressant Response', Biological Psychiatry Global Open Science, 2(2), pp. 115-126. doi: 10.1016/j.bpsgos.2021.07.008

Pain O, Hodgson K, Trubetskoy V, Ripke S, Marshe VS, Adams MJ, and sur.. Identifying the Common Genetic Basis of Antidepressant Response. Biological Psychiatry Global Open Science [Internet]. 2022 April [cited 2024 April 12];2(2):115-126. doi: 10.1016/j.bpsgos.2021.07.008

O. Pain, et al., "Identifying the Common Genetic Basis of Antidepressant Response", Biological Psychiatry Global Open Science, vol. 2, no. 2, pp. 115-126, April 2022. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:085279. [Accessed: 12 April 2024]

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Title (english)Identifying the Common Genetic Basis of Antidepressant Response
AuthorOliver Pain
AuthorKaren Hodgson
AuthorVassily Trubetskoy
AuthorStephan Ripke
AuthorVictoria S. Marshe
AuthorMark J. Adams
AuthorEnda M. Byrne
AuthorAdrian I. Campos
AuthorTania Carrillo-Roa
AuthorAnnamaria Cattaneo
AuthorThomas D. Als
AuthorDaniel Souery
AuthorMojca Z. Dernovsek
AuthorChiara Fabbri
AuthorCaroline Hayward
AuthorNeven Henigsberg
AuthorJoanna Hauser
AuthorJames L. Kennedy
AuthorEric J. Lenze
AuthorGlyn Lewis
AuthorDaniel J. Müller
AuthorNicholas G. Martin
AuthorBenoit H. Mulsant
AuthorOle Mors
AuthorNader Perroud
AuthorDavid J. Porteous
AuthorMiguel E. Rentería
AuthorCharles F. Reynolds III
AuthorMarcella Rietschel
AuthorRudolf Uher
AuthorEleanor M. Wigmore
AuthorWolfgang Maier
AuthorNaomi R. Wray
AuthorKatherine J. Aitchison
AuthorVolker Arolt
AuthorBernhard T. Baune
AuthorJoanna M. Biernacka
AuthorGuido Bondolfi
AuthorKatharina Domschke
AuthorMasaki Kato
AuthorQingqin S. Li
AuthorYu-Li Liu
AuthorAlessandro Serretti
AuthorShih-Jen Tsai
AuthorGustavo Turecki
AuthorRichard Weinshilboum
AuthorAndrew M. McIntosh
AuthorCathryn M. Lewis
CollaborationGSRD Consortium
CollaborationMajor Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Author's institutionUniversity of Zagreb
School of Medicine
(Department of Psychiatry and Psychological Medicine)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Psychiatry
Abstract (english)
Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction. ----- Methods: Genome-wide analysis of remission (n remit = 1852, n nonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism-based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA. ----- Results: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism-based heritability was significantly different from zero for remission (h 2 = 0.132, SE = 0.056) but not for percentage improvement (h 2 = -0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response. Conclusions: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleBiological Psychiatry Global Open Science
Numberingvol. 2, no. 2, pp. 115-126
p-ISSN2667-1743
DOIhttps://doi.org/10.1016/j.bpsgos.2021.07.008
URN:NBNurn:nbn:hr:105:085279
Publication2022-04
Document URLhttps://linkinghub.elsevier.com/retrieve/pii/S2667174321000859
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2022-12-06 10:32:50