Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.
Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.
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DOI：
10.1186/s13195-023-01376-6
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发表时间：
2024-01-20
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揭示语言陈述性记忆（VDM）全基因组关联研究（GWAS）结果的功能相关性可能有助于开发干预措施，以减少与年龄相关的记忆衰退和痴呆。我们对29,076名欧洲血统的老年非痴呆个体的段落（PAR-dr）和单词列表（WL-dr）延迟回忆GWAS进行了多组学和途径富集分析。我们评估了44个组织中的单变量关联和表达数量性状基因座（eQTL）以及海马中的甲基化数量性状基因座（meQTL）之间的关系。我们确定了53种组织中基因关联和转录水平之间的关系，注释为免疫基因，以及转录因子（TF）和microRNA的调控。为了确定重要的途径，在每个队列中测试基因集富集并跨队列进行荟萃分析。对通路组分基因进行脑组织差异表达分析。VDM的单变量关联显示出与所有组织中的eQTL和海马内的meQTL的显著连锁不平衡（LD）。更强的WL-dr基因关联与包括海马在内的四种脑组织中的表达减少相关。更强大的PAR-dr和/或WL-dr基因关联与免疫力错综复杂地联系在一起，并受到31个TF和2个microRNA的影响。包括I型糖尿病在内的6条通路与PAR-DR和WL-DR均表现出显著的相关性。这些通路包括15个与VDM表现密切相关的MHC基因，显示出基于脑组织认知状态的不同表达模式。VDM遗传关联通过eQTL和meQTL影响表达调控。TF、microRNA、MHC基因和免疫相关通路的参与有助于老年人的VDM表现。在线版本包含补充材料，可通过10.1186/s13195-023-01376-6获得。
Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals. The online version contains supplementary material available at 10.1186/s13195-023-01376-6.
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全基因组对言语记忆的言论性记忆的研究：基因组流行病学财团的心脏和衰老研究的同龄人。
影响因子：
10.6
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56.9
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Soboleva A