Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

Sieberts, S. K.; Perumal, T. M.; Carrasquillo, M. M.; Allen, M.; Reddy, J. S.; Hoffman, G. E.; Dang, K. K.; Calley, J.; Ebert, P. J.; Eddy, J.; Wang, X.; Greenwood, A. K.; Mostafavi, S.; the AMP-AD Consortium,; the CommonMind Consortium (CMC),; Omberg, L.; Peters, M.; Logsdon, B. A.; De Jager, P. L.; Ertekin-Taner, N.; Mangravite, L. M.

doi:10.1101/638544

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bioRxiv · 10.1101/638544

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

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Abstract

The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimers Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes), and provide the results as a community resource. We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. In addition, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a common resource for use across the community in research programs. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975).

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Sieberts, S. K., Perumal, T. M., Carrasquillo, M. M., Allen, M., Reddy, J. S., Hoffman, G. E., Dang, K. K., Calley, J., Ebert, P. J., Eddy, J., Wang, X., Greenwood, A. K., Mostafavi, S., the AMP-AD Consortium,, the CommonMind Consortium (CMC),, Omberg, L., Peters, M., Logsdon, B. A., De Jager, P. L., Ertekin-Taner, N., Mangravite, L. M.. 2019-05-17. Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions. https://doi.org/10.1101/638544

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