人类血浆中神经相关蛋白的遗传特征。

The genetic landscape of neuro-related proteins in human plasma.

机构信息

Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.

出版信息

Nat Hum Behav. 2024 Nov;8(11):2222-2234. doi: 10.1038/s41562-024-01963-z. Epub 2024 Aug 29.

Abstract

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.

摘要

了解神经相关蛋白的遗传基础对于剖析人类行为特征的分子基础以及神经精神疾病的发病机制至关重要。在这里,SCALLOP 联盟对超过 12000 个人的 184 种人类血浆神经相关蛋白进行了全基因组关联荟萃分析。该分析确定了 125 个顺式调控蛋白数量性状基因座(cis-pQTL)和 164 个反式 pQTL。映射的 pQTL 平均捕获每个蛋白遗传力的 50%。在 cis-pQTL 中,多种蛋白与人类行为特征(如饮酒和进食、吸烟和受教育程度)以及神经和精神疾病(如疼痛、神经质和精神分裂症)共享遗传基础。与已建立的药物信息相结合,因果推理分析验证了 66 个匹配的蛋白靶标和疾病或副作用与现有药物的组合中的 52 个,同时提出了数百种再利用和新的治疗靶标。

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