Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Brain expression quantitative trait locus and network analyses reveal downstream effects and putative drivers for brain-related diseases

Niek de Klein, Ellen Tsai, Martijn Vochteloo, Denis Baird, Yunfeng Huang, Chia‐Yen Chen, Sipko van Dam, Roy Oelen, Patrick Deelen, Olivier B. Bakker, Omar El Garwany, Zhengyu Ouyang, Eric Marshall, Maria I. Zavodszky, Wouter van Rheenen, Mark K. Bakker, Jan H. Veldink, Tom R. Gaunt, Heiko Runz, Lude Franke, Harm-Jan Westra

Nature Genetics · 2023

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Summary

Identification of therapeutic targets from genome-wide association studies (GWAS) requires insights into downstream functional consequences. We harmonized 8,613 RNA-sequencing samples from 14 brain datasets to create the MetaBrain resource and performed cis- and trans-expression quantitative trait locus (eQTL) meta-analyses in multiple brain region- and ancestry-specific datasets (n ≤ 2,759). Many of the 16,169 cortex cis-eQTLs were tissue-dependent when compared with blood cis-eQTLs. We inferred brain cell types for 3,549 cis-eQTLs by interaction analysis. We prioritized 186 cis-eQTLs for 31 brain-related traits using Mendelian randomization and co-localization including 40 cis-eQTLs with an inferred cell type, such as a neuron-specific cis-eQTL (CYP24A1) for multiple sclerosis. We furthe

Source type
Peer-reviewed study
DOI
10.1038/s41588-023-01300-6
Catalogue ID
SNmojad27m-sjr27i
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