Methylation QTL (mQTL) Resources#

Methylation quantitative trait loci (mQTL) identify genetic variants that influence DNA methylation levels at CpG sites. DNA methylation is a stable epigenetic mark that regulates gene expression and is implicated in aging and neurodegeneration. This resource provides mQTL summary statistics, fine-mapping results, and colocalization analyses across brain tissues from multiple AD cohorts.

Overview#

mQTL mapping was performed on EPIC or 450K array methylation data from brain tissue, using the FunGen-xQTL pipeline. Beta-values were M-value transformed, batch corrected, and adjusted for cell-type proportions and principal components before tensorQTL-based association testing. Fine-mapping was performed using SuSiE-RSS (or fSuSiE for multi-context). Pairwise colocalization with AD GWAS fine-mapping uses a novel epigenetic fine-mapping approach developed for this resource.

Available Datasets#

Brain Tissue#

Analyses Performed#

Single-Context Fine-Mapping#

Fine-mapping using SuSiE-RSS per CpG site, providing:

• Posterior inclusion probabilities (PIPs)
• 95% credible sets
• Effect sizes on methylation M-values

Multi-Context Fine-Mapping#

For ROSMAP and MSBB multi-region mQTL, fSuSiE integrates methylation signals across brain regions. Multi-context fine-mapping results are at syn69670592.

AD GWAS Colocalization#

Bulk mQTL–AD GWAS pairwise colocalization uses a novel fine-mapping approach for epigenetic data to identify methylation-level mechanisms of AD risk variants. Results available at syn69865816 and syn69670630.

Multi-Context Colocalization#

ColocBoost multi-context colocalization across mQTL datasets and cohorts is available at syn69670597.

Data Access#