Genetic regulation of cell type-specific chromatin accessibility shapes brain disease etiology.
Science
; 384(6698): eadh4265, 2024 May 24.
Article
in En
| MEDLINE
| ID: mdl-38781378
ABSTRACT
Nucleotide variants in cell type-specific gene regulatory elements in the human brain are risk factors for human disease. We measured chromatin accessibility in 1932 aliquots of sorted neurons and non-neurons from 616 human postmortem brains and identified 34,539 open chromatin regions with chromatin accessibility quantitative trait loci (caQTLs). Only 10.4% of caQTLs are shared between neurons and non-neurons, which supports cell type-specific genetic regulation of the brain regulome. Incorporating allele-specific chromatin accessibility improves statistical fine-mapping and refines molecular mechanisms that underlie disease risk. Using massively parallel reporter assays in induced excitatory neurons, we screened 19,893 brain QTLs and identified the functional impact of 476 regulatory variants. Combined, this comprehensive resource captures variation in the human brain regulome and provides insights into disease etiology.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Brain Diseases
/
Chromatin
/
Gene Expression Regulation
/
Regulatory Elements, Transcriptional
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Science
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United States