Federal Grant Award Summary

Brigham & Women's Hospital Inc. received a $177,355 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded May 15, 2026, with a completion date of April 30, 2030. This research initiative investigates the role of the X chromosome in chronic obstructive pulmonary disease (COPD) through integrated multi-omic analytical approaches. The project integrates whole genome sequencing, DNA methylation, and gene expression data from lung and blood samples across four established COPD cohorts (COPDGene, LTRC, LTCOPD, and ECLIPSE) to elucidate mechanisms by which X chromosome genetic variants influence disease susceptibility and heterogeneity.

The research deliverables include identification of epigenetic regulatory mechanisms through methylation quantitative trait loci (mQTL) and colocalization analyses (Aim 1), association of X chromosome genetic variants with gene expression through expression quantitative trait loci (eQTL) analysis (Aim 2), and comprehensive mapping of regulatory mechanisms using innovative gene regulatory network approaches that account for X chromosome dosage effects (Aim 3). The project addresses a significant gap in COPD research by examining sex-specific patterns of gene regulation, particularly regarding incomplete X chromosome inactivation (XCI) escape genes, with the objective of enhancing understanding of X chromosome gene regulation and identifying molecular mechanisms underlying COPD disease heterogeneity in female populations.