西湖大学研究论文登上Cell头条：全面解析人类大脑中的非编码RNA的遗传调控及其作用

Core Viewpoint - The research conducted by Westlake University identifies a significant number of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in the human brain, revealing their genetic control and implications for complex traits, thus providing new insights into the genetic regulatory mechanisms of non-coding RNAs in relation to brain-related complex traits [2][3][12]. Summary by Sections Research Findings - The study analyzed RNA sequencing data from 2,865 human brain cortex samples, identifying 38,441 lncRNAs and 23,548 circRNAs, with 27,453 lncRNAs and all circRNAs not included in the GENCODE database [3][6]. - It determined 15,362 lncRNAs and 1,312 circRNAs with cis-expression quantitative trait loci (eQTL), highlighting the independent nature of eQTLs for lncRNAs and circRNAs compared to their adjacent protein-coding genes [3][7]. - The research found that lncRNA-eQTL and circRNA-eQTL account for an average of 11.14% and 3.20% of the SNP heritability for 14 brain-related complex traits, respectively, compared to 17.19% for protein-coding gene eQTLs [7]. Implications for Complex Traits - The study suggests that certain lncRNAs (e.g., those near VPS45, MAPT, and RGS6) and circRNAs (e.g., those related to GRIN2A) may influence complex traits through non-coding RNA genetic regulation [3][12]. - It integrates lncRNA-eQTL and circRNA-eQTL data with genome-wide association study (GWAS) summary statistics, identifying 795 lncRNAs and 8 circRNAs associated with brain-related traits, indicating shared genetic regulatory mechanisms [7][12]. Research Context - The research addresses the challenge of understanding the molecular mechanisms behind GWAS signals, particularly focusing on non-coding regions where many trait-related variants reside [4][5]. - Previous studies have primarily focused on protein-coding genes, leaving a gap in understanding the genetic control mechanisms of non-coding RNAs, especially in the context of brain-related traits and diseases [6][12].