Genetic Architecture of Cerebrospinal Fluid and Brain Metabolite Levels and the Genetic Colocalization of Metabolites with Human Traits

Overview

Journal Nat Genet

Specialty Genetics

Date 2024 Nov 11

PMID 39528826

Authors

Ciyang Wang

Chengran Yang

Daniel Western

Muhammad Ali

Yueyao Wang

Chia-Ling Phuah

John Budde

Lihua Wang

Priyanka Gorijala

Jigyasha Timsina

Agustin Ruiz

Pau Pastor

Maria Victoria Fernandez

Daniel J Panyard

Corinne D Engelman

Yuetiva Deming

Merce Boada

Amanda Cano

Pablo Garcia-Gonzalez

Neill R Graff-Radford

Hiroshi Mori

Jae-Hong Lee

Richard J Perrin

Laura Ibanez

Yun Ju Sung

Carlos Cruchaga

Affiliations

Soon will be listed here.

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.

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