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.

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和神经精神疾病的病因至关重要。在这里，SCALLOP 联盟对 12,000 多个个体进行了全基因组关联荟萃分析，分析了人血浆中的 184 种神经相关蛋白。该分析确定了 125 个顺式调节蛋白数量性状位点 （cis-pQTL） 和 164 个反式 pQTL。定位的 pQTL 捕获了每种蛋白质平均 50% 的遗传力。在 cis-pQTL 中，多种蛋白质与人类行为特征（如酒精和食物摄入量、吸烟和教育程度）以及神经系统疾病和精神疾病（如疼痛、神经质和精神分裂症）共享遗传基础。因果推理分析与已建立的药物信息相结合，验证了 66 种蛋白质靶点和疾病或副作用与可用药物的匹配组合中的 52 种，同时提出了数百个再利用和新的治疗靶点。