Brain metabolism perturbation can contribute to traits and diseases. We conducted a genome-wide association study for cerebrospinal fluid (CSF) and brain metabolite levels, identifying 205 independent associations (47.3% new signals, containing 11 new loci) for 139 CSF metabolites, and 32 independent associations (43.8% new signals, containing 4 new loci) for 31 brain metabolites. Of these, 96.9% (CSF) and 71.4% (brain) of the new signals belonged to previously analyzed metabolites in blood or urine. We integrated the metabolite quantitative trait loci (MQTLs) with 23 neurological, psychiatric and common human traits and diseases through colocalization to identify metabolites and biological processes implicated in these phenotypes. Combining CSF and brain, we identified 71 metabolite–trait associations, such as glycerophosphocholines with Alzheimer’s disease, O-sulfo-l-tyrosine with Parkinson’s disease, glycine, xanthine with waist-to-hip ratio and ergothioneine with inflammatory bowel disease. Our study expanded the knowledge of MQTLs in the central nervous system, providing insights into human traits.

大脑新陈代谢紊乱会导致性状和疾病。我们对脑脊液 （CSF） 和脑代谢物水平进行了全基因组关联研究，确定了 139 种脑脊液代谢物的 205 个独立关联 （47.3% 新信号，包含 11 个新基因座），以及 31 种脑代谢物的 32 个独立关联 （43.8% 新信号，包含 4 个新基因座）。其中，96.9% （CSF） 和 71.4% （大脑） 的新信号属于先前分析的血液或尿液中的代谢物。我们通过共定位将代谢物数量性状位点 （MQTLs） 与 23 种神经、精神病学和常见人类性状和疾病整合在一起，以鉴定与这些表型相关的代谢物和生物过程。结合脑脊液和大脑，我们确定了 71 个代谢物-性状关联，例如甘油磷酸胆碱与阿尔茨海默病、O-sulfo-l-酪氨酸与帕金森病、甘氨酸、黄嘌呤与腰臀比和麦角硫因与炎症性肠病。我们的研究扩展了中枢神经系统中 MQTL 的知识，提供了对人类特征的见解。