Description

This study constructs the largest brain-centric xQTL atlas to date, spanning five molecular phenotypes (expression, splicing, protein abundance, DNA methylation, histone acetylation) across 13 brain regions and 7 cell types from thousands of individuals in four cohorts (ROSMAP, MSBB, Knight-ADRC, MiGA). All xQTLs were generated using standardized pipelines developed by the FunGen-AD xQTL Workgroup with stringent quality control. The results were harmonized using a common set of ADSP genomic references.

The overall goal is to create a unified, high-coverage xQTL resource that improves on existing datasets in both scope and usability. To enhance detection of regulatory variants, cis testing windows leveraged tissue-specific topologically associating domains (TADs) instead of conventional fixed 1 Mb windows, identifying ~40% more QTL associations while enriching for variants with regulatory potential.

Principal Investigators

  • Philip L. De Jager — Columbia University Medical Center
  • Gao Wang — Columbia University
  • Carlos Cruchaga — Washington University School of Medicine in St. Louis
  • Yuk Yee (Fanny) Leung — University of Pennsylvania Perelman School of Medicine

Funding Sources

U01AG072572, R01AG086467, U01AG072577, R01AG076901, U01AG072572, RF1AG066107, R01AG067501, R01AG086467, U01AG072577, R01AG080810, U01AG058654, R35GM146868, U01AG058635