Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes

Abstract Achieving remission following initial antidepressant therapy in patients with major depressive disorder (MDD) is an important clinical result. Making predictions based on genetic markers holds promise for improving the remission rate. However, genetic variants found in previous genetic stud...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jong-Ho Park, Shinn-Won Lim, Woojae Myung, Inho Park, Hyeok-Jae Jang, Seonwoo Kim, Min-Soo Lee, Hun Soo Chang, DongHo Yum, Yeon-Lim Suh, Jong-Won Kim, Doh Kwan Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cf984e96a1be4c26843a60ae3dc49776
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cf984e96a1be4c26843a60ae3dc49776
record_format	dspace
spelling	oai:doaj.org-article:cf984e96a1be4c26843a60ae3dc497762021-12-02T13:20:21ZWhole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes10.1038/s41598-021-83887-62045-2322https://doaj.org/article/cf984e96a1be4c26843a60ae3dc497762021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83887-6https://doaj.org/toc/2045-2322Abstract Achieving remission following initial antidepressant therapy in patients with major depressive disorder (MDD) is an important clinical result. Making predictions based on genetic markers holds promise for improving the remission rate. However, genetic variants found in previous genetic studies do not provide robust evidence to aid pharmacogenetic decision-making in clinical settings. Thus, the objective of this study was to perform whole-genome sequencing (WGS) using genomic DNA to identify genetic variants associated with the treatment outcomes of selective serotonin reuptake inhibitors (SSRIs). We performed WGS on 100 patients with MDD who were treated with escitalopram (discovery set: 36 remitted and 64 non-remitted). The findings were applied to an additional 553 patients with MDD who were treated with SSRIs (replication set: 185 remitted and 368 non-remitted). A novel loss-of-function variant (rs3213755) in keratin-associated protein 1–1 (KRTAP1-1) was identified in this study. This rs3213755 variant was significantly associated with remission following antidepressant treatment (p = 0.0184, OR 3.09, 95% confidence interval [CI] 1.22–7.80 in the discovery set; p = 0.00269, OR 1.75, 95% CI 1.22–2.53 in the replication set). Moreover, the expression level of KRTAP1-1 in surgically resected human temporal lobe samples was significantly associated with the rs3213755 genotype. WGS studies on a larger sample size in various ethnic groups are needed to investigate genetic markers useful in the pharmacogenetic prediction of remission following antidepressant treatment.Jong-Ho ParkShinn-Won LimWoojae MyungInho ParkHyeok-Jae JangSeonwoo KimMin-Soo LeeHun Soo ChangDongHo YumYeon-Lim SuhJong-Won KimDoh Kwan KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jong-Ho Park Shinn-Won Lim Woojae Myung Inho Park Hyeok-Jae Jang Seonwoo Kim Min-Soo Lee Hun Soo Chang DongHo Yum Yeon-Lim Suh Jong-Won Kim Doh Kwan Kim Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes
description	Abstract Achieving remission following initial antidepressant therapy in patients with major depressive disorder (MDD) is an important clinical result. Making predictions based on genetic markers holds promise for improving the remission rate. However, genetic variants found in previous genetic studies do not provide robust evidence to aid pharmacogenetic decision-making in clinical settings. Thus, the objective of this study was to perform whole-genome sequencing (WGS) using genomic DNA to identify genetic variants associated with the treatment outcomes of selective serotonin reuptake inhibitors (SSRIs). We performed WGS on 100 patients with MDD who were treated with escitalopram (discovery set: 36 remitted and 64 non-remitted). The findings were applied to an additional 553 patients with MDD who were treated with SSRIs (replication set: 185 remitted and 368 non-remitted). A novel loss-of-function variant (rs3213755) in keratin-associated protein 1–1 (KRTAP1-1) was identified in this study. This rs3213755 variant was significantly associated with remission following antidepressant treatment (p = 0.0184, OR 3.09, 95% confidence interval [CI] 1.22–7.80 in the discovery set; p = 0.00269, OR 1.75, 95% CI 1.22–2.53 in the replication set). Moreover, the expression level of KRTAP1-1 in surgically resected human temporal lobe samples was significantly associated with the rs3213755 genotype. WGS studies on a larger sample size in various ethnic groups are needed to investigate genetic markers useful in the pharmacogenetic prediction of remission following antidepressant treatment.
format	article
author	Jong-Ho Park Shinn-Won Lim Woojae Myung Inho Park Hyeok-Jae Jang Seonwoo Kim Min-Soo Lee Hun Soo Chang DongHo Yum Yeon-Lim Suh Jong-Won Kim Doh Kwan Kim
author_facet	Jong-Ho Park Shinn-Won Lim Woojae Myung Inho Park Hyeok-Jae Jang Seonwoo Kim Min-Soo Lee Hun Soo Chang DongHo Yum Yeon-Lim Suh Jong-Won Kim Doh Kwan Kim
author_sort	Jong-Ho Park
title	Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes
title_short	Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes
title_full	Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes
title_fullStr	Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes
title_full_unstemmed	Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes
title_sort	whole-genome sequencing reveals krtap1-1 as a novel genetic variant associated with antidepressant treatment outcomes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cf984e96a1be4c26843a60ae3dc49776
work_keys_str_mv	AT jonghopark wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT shinnwonlim wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT woojaemyung wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT inhopark wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT hyeokjaejang wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT seonwookim wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT minsoolee wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT hunsoochang wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT donghoyum wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT yeonlimsuh wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT jongwonkim wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes AT dohkwankim wholegenomesequencingrevealskrtap11asanovelgeneticvariantassociatedwithantidepressanttreatmentoutcomes
_version_	1718393239754506240

Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes

Ejemplares similares