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Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data

It is well-accepted that both environment and genetic factors contribute to the development of mental disorders (MD). However, few genetic studies used time-to-event data analysis to identify the susceptibility genetic variants associated with MD and explore the role of environment factors in these...

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Autores principales: Meng, Peilin, Ye, Jing, Chu, Xiaomeng, Cheng, Bolun, Cheng, Shiqiang, Liu, Li, Yang, Xuena, Liang, Chujun, Zhang, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752606/
https://www.ncbi.nlm.nih.gov/pubmed/35017462
http://dx.doi.org/10.1038/s41398-022-01782-8
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author Meng, Peilin
Ye, Jing
Chu, Xiaomeng
Cheng, Bolun
Cheng, Shiqiang
Liu, Li
Yang, Xuena
Liang, Chujun
Zhang, Feng
author_facet Meng, Peilin
Ye, Jing
Chu, Xiaomeng
Cheng, Bolun
Cheng, Shiqiang
Liu, Li
Yang, Xuena
Liang, Chujun
Zhang, Feng
author_sort Meng, Peilin
collection PubMed
description It is well-accepted that both environment and genetic factors contribute to the development of mental disorders (MD). However, few genetic studies used time-to-event data analysis to identify the susceptibility genetic variants associated with MD and explore the role of environment factors in these associations. In order to detect novel genetic loci associated with MD based on the time-to-event data and identify the role of environmental factors in them, this study recruited 376,806 participants from the UK Biobank cohort. The MD outcomes (including overall MD status, anxiety, depression and substance use disorders (SUD)) were defined based on in-patient hospital, self-reported and death registry data collected in the UK Biobank. SPACOX approach was used to identify the susceptibility loci for MD using the time-to-event data of the UK Biobank cohort. And then we estimated the associations between identified candidate loci, fourteen environment factors and MD through a phenome-wide association study and mediation analysis. SPACOX identified multiple candidate loci for overall MD status, depression and SUD, such as rs139813674 (P value = 8.39 × 10(–9), ZNF684) for overall MD status, rs7231178 (DCC, P value = 2.11 × 10(–9)) for depression, and rs10228494 (FOXP2, P value = 6.58 × 10(–10)) for SUD. Multiple environment factors could influence the associations between identified loci and MD, such as confide in others and felt hated. Our study identified novel candidate loci for MD, highlighting the strength of time-to-event data based genetic association studies. We also observed that multiple environment factors could influence the association between susceptibility loci and MD.
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spelling pubmed-87526062022-01-20 Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data Meng, Peilin Ye, Jing Chu, Xiaomeng Cheng, Bolun Cheng, Shiqiang Liu, Li Yang, Xuena Liang, Chujun Zhang, Feng Transl Psychiatry Article It is well-accepted that both environment and genetic factors contribute to the development of mental disorders (MD). However, few genetic studies used time-to-event data analysis to identify the susceptibility genetic variants associated with MD and explore the role of environment factors in these associations. In order to detect novel genetic loci associated with MD based on the time-to-event data and identify the role of environmental factors in them, this study recruited 376,806 participants from the UK Biobank cohort. The MD outcomes (including overall MD status, anxiety, depression and substance use disorders (SUD)) were defined based on in-patient hospital, self-reported and death registry data collected in the UK Biobank. SPACOX approach was used to identify the susceptibility loci for MD using the time-to-event data of the UK Biobank cohort. And then we estimated the associations between identified candidate loci, fourteen environment factors and MD through a phenome-wide association study and mediation analysis. SPACOX identified multiple candidate loci for overall MD status, depression and SUD, such as rs139813674 (P value = 8.39 × 10(–9), ZNF684) for overall MD status, rs7231178 (DCC, P value = 2.11 × 10(–9)) for depression, and rs10228494 (FOXP2, P value = 6.58 × 10(–10)) for SUD. Multiple environment factors could influence the associations between identified loci and MD, such as confide in others and felt hated. Our study identified novel candidate loci for MD, highlighting the strength of time-to-event data based genetic association studies. We also observed that multiple environment factors could influence the association between susceptibility loci and MD. Nature Publishing Group UK 2022-01-11 /pmc/articles/PMC8752606/ /pubmed/35017462 http://dx.doi.org/10.1038/s41398-022-01782-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Meng, Peilin
Ye, Jing
Chu, Xiaomeng
Cheng, Bolun
Cheng, Shiqiang
Liu, Li
Yang, Xuena
Liang, Chujun
Zhang, Feng
Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data
title Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data
title_full Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data
title_fullStr Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data
title_full_unstemmed Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data
title_short Associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the UK Biobank data
title_sort associations between genetic loci, environment factors and mental disorders: a genome-wide survival analysis using the uk biobank data
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752606/
https://www.ncbi.nlm.nih.gov/pubmed/35017462
http://dx.doi.org/10.1038/s41398-022-01782-8
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