Targeted, High-Resolution RNA Sequencing of Non-coding Genomic Regions Associated With Neuropsychiatric Functions
In conclusion, this study substantially expands the transcriptome annotations for regions of the genome associated with important neuropsychiatric traits, including diseases like Alzheimer’s, Parkinson’s and schizophrenia. These transcriptomes collectively comprise a valuable atlas that can be used to connect gene expression with neuropsychiatric traits. Ultimately, novel transcripts identified herein could act as biomarkers for disease or potential therapeutic targets.
Materials and Methods
Selection of GWAS Haplotype Blocks
The complete GWAS database was downloaded from the NHGRI catalog (Welter et al., 2013; Macarthur et al., 2017), then filtered to include only studies with a sample size of n ≥ 1000 that focused on traits associated with the brain (including behavioral traits, mental illness, as well as neuropsychiatric disorders like Alzheimer’s, Parkinson’s and schizophrenia). Since GWAS simply associates traits with regions of the genome that are in LD, the causative SNP could be anywhere within the region of LD. In order to ensure the causative SNP is included, it is necessary to capture the full haplotype block associated with the SNP reported by GWAS. As such, we used SNAP (Johnson et al., 2008) to identify all SNPs in LD, with an LD threshold of R> 0.5 and a maximum distance between SNPs of 500 kb. All SNPs in LD were then assumed to comprise a single haplotype block. This resulted in 1,323 haplotype blocks comprising a total o...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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