Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,351 bioRxiv papers from 296,699 authors.
Bipolar disorder (BD) affects the quality of life of approximately 1% of the population and represents a major public health concern. It is known to be highly heritable but large-scale genome-wide association studies (GWAS) have discovered only a handful of markers associated with the disease. Furthermore, the biological mechanisms underlying these markers need to be elucidated. We recently published a gene-level association test, PrediXcan that integrates transcriptome regulation data to characterize the function of these markers in a tissue specific manner. In this study, we developed prediction models for mRNA levels in 10 brain regions using data from the GTEx project and performed PrediXcan analysis in WTCCC as well as in an independent cohort, GAIN. We replicate the association between predicted expression of PTPRE and BD risk in whole blood and recapitulate the association in brain tissues. PTPRE encodes the protein tyrosine phosphatase, receptor type E, that is known to be involved in RAS signaling and activation of voltage-gated K+ channels. We also found a new genome-wide significant association between lower predicted expression of BBX (bobby sox homolog) in the anterior cingulate cortex region of the brain and increased risk of BD (pWTCCC = 7.02 x 10e-6, pGAIN = 4.68 x 10e-3, pmeta = 1.11 x 10e-7). In sum, we used our mechanistically informed approach, PrediXcan, to identify and replicate two novel genome-wide significant genes using existing GWAS studies.
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