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Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers

BACKGROUND: The clinical heterogeneity in major depressive disorder (MDD), variable treatment response, and conflicting findings limit the ability of genomics toward the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to eva...

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Autores principales: Singh, Priyanka, Srivastava, Ankit, Guin, Debleena, Thakran, Sarita, Yadav, Jyoti, Chandna, Puneet, Sood, Mamta, Chadda, Rakesh Kumar, Kukreti, Ritushree
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586057/
https://www.ncbi.nlm.nih.gov/pubmed/36655406
http://dx.doi.org/10.1093/ijnp/pyad001
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author Singh, Priyanka
Srivastava, Ankit
Guin, Debleena
Thakran, Sarita
Yadav, Jyoti
Chandna, Puneet
Sood, Mamta
Chadda, Rakesh Kumar
Kukreti, Ritushree
author_facet Singh, Priyanka
Srivastava, Ankit
Guin, Debleena
Thakran, Sarita
Yadav, Jyoti
Chandna, Puneet
Sood, Mamta
Chadda, Rakesh Kumar
Kukreti, Ritushree
author_sort Singh, Priyanka
collection PubMed
description BACKGROUND: The clinical heterogeneity in major depressive disorder (MDD), variable treatment response, and conflicting findings limit the ability of genomics toward the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to evaluate potential variants for clinical translation. METHODS: We systematically reviewed all candidates and genome-wide association studies for both MDD susceptibility and antidepressant response, independently, using MEDLINE, particularly to identify replicated findings. These variants were evaluated for functional consequences using different in silico tools and further estimated their diagnostic predictability by calculating positive predictive values. RESULTS: A total of 217 significantly associated studies comprising 1200 variants across 545 genes and 128 studies including 921 variants across 412 genes were included with MDD susceptibility and antidepressant response, respectively. Although the majority of associations were confirmed by a single study, we identified 31 and 18 replicated variants (in at least 2 studies) for MDD and antidepressant response. Functional annotation of these 31 variants predicted 20% coding variants as deleterious/damaging and 80.6% variants with regulatory effect. Similarly, the response-related 18 variants revealed 25% coding variant as damaging and 88.2% with substantial regulatory potential. Finally, we could calculate the diagnostic predictability of 19 and 5 variants whose positive predictive values ranges from 0.49 to 0.66 for MDD and 0.36 to 0.66 for response. CONCLUSIONS: The replicated variants presented in our data are promising for disease diagnosis and improved response outcomes. Although these quantitative assessment measures are solely directive of available observational evidence, robust homogenous validation studies are required to strengthen these variants for molecular diagnostic application.
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spelling pubmed-105860572023-10-20 Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers Singh, Priyanka Srivastava, Ankit Guin, Debleena Thakran, Sarita Yadav, Jyoti Chandna, Puneet Sood, Mamta Chadda, Rakesh Kumar Kukreti, Ritushree Int J Neuropsychopharmacol Regular Research Articles BACKGROUND: The clinical heterogeneity in major depressive disorder (MDD), variable treatment response, and conflicting findings limit the ability of genomics toward the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to evaluate potential variants for clinical translation. METHODS: We systematically reviewed all candidates and genome-wide association studies for both MDD susceptibility and antidepressant response, independently, using MEDLINE, particularly to identify replicated findings. These variants were evaluated for functional consequences using different in silico tools and further estimated their diagnostic predictability by calculating positive predictive values. RESULTS: A total of 217 significantly associated studies comprising 1200 variants across 545 genes and 128 studies including 921 variants across 412 genes were included with MDD susceptibility and antidepressant response, respectively. Although the majority of associations were confirmed by a single study, we identified 31 and 18 replicated variants (in at least 2 studies) for MDD and antidepressant response. Functional annotation of these 31 variants predicted 20% coding variants as deleterious/damaging and 80.6% variants with regulatory effect. Similarly, the response-related 18 variants revealed 25% coding variant as damaging and 88.2% with substantial regulatory potential. Finally, we could calculate the diagnostic predictability of 19 and 5 variants whose positive predictive values ranges from 0.49 to 0.66 for MDD and 0.36 to 0.66 for response. CONCLUSIONS: The replicated variants presented in our data are promising for disease diagnosis and improved response outcomes. Although these quantitative assessment measures are solely directive of available observational evidence, robust homogenous validation studies are required to strengthen these variants for molecular diagnostic application. Oxford University Press 2023-01-19 /pmc/articles/PMC10586057/ /pubmed/36655406 http://dx.doi.org/10.1093/ijnp/pyad001 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of CINP. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Research Articles
Singh, Priyanka
Srivastava, Ankit
Guin, Debleena
Thakran, Sarita
Yadav, Jyoti
Chandna, Puneet
Sood, Mamta
Chadda, Rakesh Kumar
Kukreti, Ritushree
Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers
title Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers
title_full Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers
title_fullStr Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers
title_full_unstemmed Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers
title_short Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers
title_sort genetic landscape of major depressive disorder: assessment of potential diagnostic and antidepressant response markers
topic Regular Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586057/
https://www.ncbi.nlm.nih.gov/pubmed/36655406
http://dx.doi.org/10.1093/ijnp/pyad001
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