Unique genetic architecture of CSF and brain metabolites pinpoints the novel targets for the traits of human wellness
Abstract
Brain metabolism perturbation can contribute to traits and diseases. We conducted the first large-scale CSF and brain genome-wide association studies, which identified 219 independent associations (59.8% novel) for 144 CSF metabolites and 36 independent associations (55.6% novel) for 34 brain metabolites. Most of the novel signals (97.7% and 70.0% in CSF and brain) were tissue specific. We also integrated MWAS-FUSION approaches with Mendelian Randomization and colocalization to identify causal metabolites for 27 brain and human wellness phenotypes and identified eight metabolites to be causal for eight traits (11 relationships). Low mannose level was causal to bipolar disorder and as dietary supplement it may provide therapeutic benefits. Low galactosylglycerol level was found causal to Parkinson’s Disease (PD). Our study expanded the knowledge of MQTL in central nervous system, provided insights into human wellness, and successfully demonstrates the utility of combined statistical approaches to inform interventions.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 09, 2023
- Source ID
- 10.21203/rs.3.rs-2923409/v1
Entities
People
- Agustín Ruíz
- Amanda Cano
- Carlos Cruchaga
- Chengran Yang
- Ciyang Wang
- Corinne Engelman
- Daniel J. Panyard
- Daniel Western
- Dominantly Inherited Alzheimer Network (dian)
- Hiroshi Mori
- Jae-hong Lee
- Jigyasha Timsina
- Lihua Wang
- Maria Victoria Fernandez
- Mercè Boada
- Muhammad Ali
- Neill Graff-radford
- Pablo García‐González
- Pau Pastor
- Priyanka Gorijala
- Richard J Perrin
- The Alzheimer's Disease Neuroimaging Initiative (adni)
- Yuetiva Deming
- Yun Ju Sung
Organizations
- Fundació ACE
- International University of Catalonia
- Mayo Clinic
- Stanford University
- University of Ulsan
- University of Wisconsin–Madison
- Washington University in St. Louis