Preprint: Modeling cis-regulatory variation in human brain enhancers across a large Parkinson's Disease cohort
WHY IT MATTERS
This research could eventually help doctors predict who is at highest genetic risk for Parkinson's disease and identify new drug targets by showing exactly how disease-linked genetic variations disrupt brain cell function.
Scientists studied DNA samples and brain cells from 190 people—115 without Parkinson's disease and 75 with it—to understand how genetic differences affect how brain cells work. They used advanced technology to read entire genomes and map which genes are active in different brain cell types. This research helps explain how over 100 genetic risk factors discovered in previous studies actually increase someone's chance of developing Parkinson's disease.
Modeling cis-regulatory variation in human brain enhancers across a large Parkinson's Disease cohort Authors: Sigalova, O. M. et al. Server: bioRxiv Category: genomics Abstract: Genome-wide association studies (GWAS) have linked more than a hundred non-coding genomic loci to Parkinsons disease (PD) risk. Deciphering their functional impact on gene regulation requires cell type-aware modeling approaches to assess the effects of sequence variation on enhancer function and target gene expression. To address this challenge, we generated a comprehensive matched dataset from 190 human donors (115 controls and 75 PD), comprising long-read whole-genome sequencing alongside single nucleus multiome atlases (snATAC-seq and snRNA-seq for 3.1 and 1.1 million nuclei respectively) o