Faculty, Staff and Student Publications
Language
English
Publication Date
12-1-2024
Journal
Nature Genetics
DOI
10.1038/s41588-024-01973-7
PMID
39528826
PMCID
PMC12090064
PubMedCentral® Posted Date
12-1-2025
PubMedCentral® Full Text Version
Author MSS
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.
Keywords
Humans, Quantitative Trait Loci, Genome-Wide Association Study, Brain, Alzheimer Disease, Polymorphism, Single Nucleotide, Xanthine, Phenotype, Glycine, Metabolome, Waist-Hip Ratio, Parkinson Disease, Tyrosine, Male
Published Open-Access
yes
Recommended Citation
Wang, Ciyang; Yang, Chengran; Western, Daniel; et al., "Genetic Architecture of Cerebrospinal Fluid and Brain Metabolite Levels and the Genetic Colocalization of Metabolites With Human Traits" (2024). Faculty, Staff and Student Publications. 1200.
https://digitalcommons.library.tmc.edu/uthsph_docs/1200