Gene-based association analysis identifies 190 genes affecting neuroticism

Abstract Neuroticism is a personality trait, which is an important risk factor for psychiatric disorders. Recent genome-wide studies reported about 600 genes potentially influencing neuroticism. Little is known about the mechanisms of their action. Here, we aimed to conduct a more detailed analysis...

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Autores principales:	Nadezhda M. Belonogova, Irina V. Zorkoltseva, Yakov A. Tsepilov, Tatiana I. Axenovich
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ec48653be964185b3ede6d285f3db80
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spelling	oai:doaj.org-article:8ec48653be964185b3ede6d285f3db802021-12-02T10:48:13ZGene-based association analysis identifies 190 genes affecting neuroticism10.1038/s41598-021-82123-52045-2322https://doaj.org/article/8ec48653be964185b3ede6d285f3db802021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82123-5https://doaj.org/toc/2045-2322Abstract Neuroticism is a personality trait, which is an important risk factor for psychiatric disorders. Recent genome-wide studies reported about 600 genes potentially influencing neuroticism. Little is known about the mechanisms of their action. Here, we aimed to conduct a more detailed analysis of genes that can regulate the level of neuroticism. Using UK Biobank-based GWAS summary statistics, we performed a gene-based association analysis using four sets of within-gene variants, each set possessing specific protein-coding properties. To guard against the influence of strong GWAS signals outside the gene, we used a specially designed procedure called “polygene pruning”. As a result, we identified 190 genes associated with neuroticism due to the effect of within-gene variants rather than strong GWAS signals outside the gene. Thirty eight of these genes are new. Within all genes identified, we distinguished two slightly overlapping groups obtained from using protein-coding and non-coding variants. Many genes in the former group included potentially pathogenic variants. For some genes in the latter group, we found evidence of pleiotropy with gene expression. Using a bioinformatics analysis, we prioritized the neuroticism genes and showed that the genes that contribute to neuroticism through their within-gene variants are the most appropriate candidate genes.Nadezhda M. BelonogovaIrina V. ZorkoltsevaYakov A. TsepilovTatiana I. AxenovichNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadezhda M. Belonogova Irina V. Zorkoltseva Yakov A. Tsepilov Tatiana I. Axenovich Gene-based association analysis identifies 190 genes affecting neuroticism
description	Abstract Neuroticism is a personality trait, which is an important risk factor for psychiatric disorders. Recent genome-wide studies reported about 600 genes potentially influencing neuroticism. Little is known about the mechanisms of their action. Here, we aimed to conduct a more detailed analysis of genes that can regulate the level of neuroticism. Using UK Biobank-based GWAS summary statistics, we performed a gene-based association analysis using four sets of within-gene variants, each set possessing specific protein-coding properties. To guard against the influence of strong GWAS signals outside the gene, we used a specially designed procedure called “polygene pruning”. As a result, we identified 190 genes associated with neuroticism due to the effect of within-gene variants rather than strong GWAS signals outside the gene. Thirty eight of these genes are new. Within all genes identified, we distinguished two slightly overlapping groups obtained from using protein-coding and non-coding variants. Many genes in the former group included potentially pathogenic variants. For some genes in the latter group, we found evidence of pleiotropy with gene expression. Using a bioinformatics analysis, we prioritized the neuroticism genes and showed that the genes that contribute to neuroticism through their within-gene variants are the most appropriate candidate genes.
format	article
author	Nadezhda M. Belonogova Irina V. Zorkoltseva Yakov A. Tsepilov Tatiana I. Axenovich
author_facet	Nadezhda M. Belonogova Irina V. Zorkoltseva Yakov A. Tsepilov Tatiana I. Axenovich
author_sort	Nadezhda M. Belonogova
title	Gene-based association analysis identifies 190 genes affecting neuroticism
title_short	Gene-based association analysis identifies 190 genes affecting neuroticism
title_full	Gene-based association analysis identifies 190 genes affecting neuroticism
title_fullStr	Gene-based association analysis identifies 190 genes affecting neuroticism
title_full_unstemmed	Gene-based association analysis identifies 190 genes affecting neuroticism
title_sort	gene-based association analysis identifies 190 genes affecting neuroticism
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8ec48653be964185b3ede6d285f3db80
work_keys_str_mv	AT nadezhdambelonogova genebasedassociationanalysisidentifies190genesaffectingneuroticism AT irinavzorkoltseva genebasedassociationanalysisidentifies190genesaffectingneuroticism AT yakovatsepilov genebasedassociationanalysisidentifies190genesaffectingneuroticism AT tatianaiaxenovich genebasedassociationanalysisidentifies190genesaffectingneuroticism
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Gene-based association analysis identifies 190 genes affecting neuroticism

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