TY - CONF

T1 - List of 190 genes affecting neuroticism prioritized by a new gene-based association analysis framework

AU - Belonogova, Nadezhda M.

AU - Zorkoltseva, Irina V.

AU - Цепилов, Яков Александрович

AU - Аксенович, Татьяна Иосифовна

N1 - Conference code: 54

PY - 2022

Y1 - 2022

N2 - Introduction: Recent genome-wide association studies have reported that neuroticism is influenced by about 600 genes. Little is known about the mechanisms of their action. We aimed to conduct a more detailed analysis of genes that can regulate the level of neuroticism.Materials and Methods: 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”.Results: 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. Twenty three genes were identified using protein-coding SNPs, 16 of them included potentially pathogenic variants. For 14 neuroticism genes identified using noncoding SNPs, we found evidence of pleiotropy with gene expression. Using a bioinformatics analysis, we showed that candidate genes confirmed in our study are more relevant and specific to neuroticism in their functions than non-confirmed genes.Conclusions: We prioritized the neuroticism genes and showed that the genes that contribute to neuroticism with their within-gene variants are the most appropriate candidate genes. This work was supported by the Russian Foundation for Basic Research (20-04-00464) and the Ministry of Education and Science of the RF (project 0259-2021-0009/АААА-А17-117092070032-4 and the 5-100 Excellence Program).

AB - Introduction: Recent genome-wide association studies have reported that neuroticism is influenced by about 600 genes. Little is known about the mechanisms of their action. We aimed to conduct a more detailed analysis of genes that can regulate the level of neuroticism.Materials and Methods: 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”.Results: 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. Twenty three genes were identified using protein-coding SNPs, 16 of them included potentially pathogenic variants. For 14 neuroticism genes identified using noncoding SNPs, we found evidence of pleiotropy with gene expression. Using a bioinformatics analysis, we showed that candidate genes confirmed in our study are more relevant and specific to neuroticism in their functions than non-confirmed genes.Conclusions: We prioritized the neuroticism genes and showed that the genes that contribute to neuroticism with their within-gene variants are the most appropriate candidate genes. This work was supported by the Russian Foundation for Basic Research (20-04-00464) and the Ministry of Education and Science of the RF (project 0259-2021-0009/АААА-А17-117092070032-4 and the 5-100 Excellence Program).

UR - https://www.nature.com/articles/s41431-021-01026-1

M3 - Paper

SP - P24.042.A

T2 - 54TH EUROPEAN SOCIETY OF HUMAN GENETICS

Y2 - 28 August 2021 through 31 August 2021

ER -