美国圣路易斯华盛顿大学Carlos Cruchaga小组，揭示了脑脊液和大脑代谢物水平的遗传结构，及代谢物与人类特征的遗传共定位。相关论文于2024年11月11日在线发表于国际学术期刊《自然—遗传学》。

研究人员进行了脑脊液（CSF）和大脑代谢物水平的全基因组关联研究，识别了139种脑脊液代谢物的205个独立关联（47.3%为新信号，包含11个新位点），以及31种大脑代谢物的32个独立关联（43.8%为新信号，包含4个新位点）。其中，96.9%（脑脊液）和71.4%（大脑）的新信号属于先前在血液或尿液中分析过的代谢物。

研究人员通过共定位将代谢物定量性状基因座（MQTL），与23种神经学、精神病学及常见人类特征和疾病相结合，识别了与这些表型相关的代谢物和生物过程。结合脑脊液和大脑，研究人员识别了71个代谢物-特征关联，例如甘油磷脂胆碱与阿尔茨海默病、O-硫酸化酪氨酸与帕金森病、甘氨酸、黄嘌呤与腰臀比以及麦角硫氨酸与炎症性肠病。

该研究拓展了中枢神经系统中MQTL的知识，为理解人类特征提供了新的见解。

附：英文原文

Title: Genetic architecture of cerebrospinal fluid and brain metabolite levels and the genetic colocalization of metabolites with human traits

Author: Wang, Ciyang, Yang, Chengran, Western, Daniel, Ali, Muhammad, Wang, Yueyao, Phuah, Chia-Ling, Budde, John, Wang, Lihua, Gorijala, Priyanka, Timsina, Jigyasha, Ruiz, Agustin, Pastor, Pau, Fernandez, Maria Victoria, Panyard, Daniel J., Engelman, Corinne D., Deming, Yuetiva, Boada, Merce, Cano, Amanda, Garcia-Gonzalez, Pablo, Graff-Radford, Neill R., Mori, Hiroshi, Lee, Jae-Hong, Perrin, Richard J., Ibanez, Laura, Sung, Yun Ju, Cruchaga, Carlos

Issue&Volume: 2024-11-11

Abstract: 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.

DOI: 10.1038/s41588-024-01973-7

Source: https://www.nature.com/articles/s41588-024-01973-7