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Abstract Parkinson’s Disease (PD) is a debilitating neurodegenerative disorder, characterized by motor and cognitive impairments, that affects >1% of the population over the age of 60. The pathogenesis of PD is complex and remains largely unknown. Due to the cellular heterogeneity of the human brain and changes in cell type composition with disease progression, this complexity cannot be fully captured with bulk tissue studies. To address this, we generated single-nucleus RNA sequencing and whole-genome sequencing data from 100 postmortem cases and controls, carefully selected to represent the entire spectrum of PD neuropathological severity and diverse clinical symptoms. The single nucleus data were generated from five brain regions, capturing the subcortical and cortical spread of PD pathology. Rigorous preprocessing and quality control were applied to ensure data reliability. Committed to collaborative research and open science, this dataset is available on the AMP PD Knowledge Platform, offering researchers a valuable tool to explore the molecular bases of PD and accelerate advances in understanding and treating the disease.

Motivation By testing for associations between DNA genotypes and gene expression levels, expression quantitative trait locus (eQTL) analyses have been instrumental in understanding how thousands of single nucleotide variants (SNVs) may affect gene expression. As compared to DNA genotypes, RNA genetic variation represents a phenotypic trait that reflects the actual allele content of the studied system. RNA genetic variation at expressed SNV loci can be estimated using the proportion of alleles bearing the variant nucleotide (variant allele fraction, VAFRNA). VAFRNA is a continuous measure which allows for precise allele quantitation in loci where the RNA alleles do not scale with the genotype count. We describe a method to correlate VAFRNA with gene expression and assess its ability to identify genetically regulated expression solely from RNA-sequencing (RNA-seq) datasets. Results We introduce ReQTL, an eQTL modification which substitutes the DNA allele count for the variant allele fraction at expressed SNV loci in the transcriptome (VAFRNA). We exemplify the method on sets of RNA-seq data from human tissues obtained though the Genotype-Tissue Expression (GTEx) project and demonstrate that ReQTL analyses are computationally feasible and can identify a subset of expressed eQTL loci. Availability and implementation A toolkit to perform ReQTL analyses is available at https://github.com/HorvathLab/ReQTL. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]