Chromatin Accessibility QTL (caQTL) Resources#

Chromatin accessibility quantitative trait loci (caQTL) identify genetic variants that influence open chromatin regions measured by ATAC-seq or snATAC-seq. Open chromatin marks active regulatory elements (promoters, enhancers, insulators) and caQTLs can reveal the functional impact of non-coding genetic variants on gene regulation. This resource provides single-nucleus caQTL summary statistics, fine-mapping results, and colocalization analyses in AD-relevant brain cell types.

Overview#

caQTL mapping was performed on single-nucleus ATAC-seq (snATAC-seq) data from brain tissue using the FunGen-xQTL pipeline. Peak-level chromatin accessibility was quantified per cell type, normalized, and adjusted for covariates before tensorQTL-based association testing. Fine-mapping was performed using SuSiE-RSS or fSuSiE. Pairwise colocalization with AD GWAS uses a novel epigenetic fine-mapping approach to identify chromatin-level regulatory mechanisms of AD risk variants at cell-type resolution.

Available Datasets#

Brain Tissue — Single-Nucleus#

Analyses Performed#

Single-Context Fine-Mapping#

Fine-mapping using SuSiE-RSS per ATAC-seq peak and cell type, providing:

• Posterior inclusion probabilities (PIPs)
• 95% credible sets
• Effect sizes on chromatin accessibility

caQTL–eQTL Pairwise Colocalization#

Pairwise SuSiE-COLOC analyses examine the relationship between chromatin accessibility QTLs and expression QTLs to identify regulatory variants acting through open chromatin. Results are available at syn69670597.

AD GWAS Colocalization#

Single-nucleus caQTL–AD GWAS pairwise colocalization uses the epigenetic fine-mapping approach to identify cell-type-specific chromatin accessibility mechanisms of AD genetic risk. Results available at syn69865816 and syn69670630.

Multi-Context Colocalization#

ColocBoost multi-context colocalization across caQTL cell types and eQTL datasets is available at syn69670597.

Data Access#