# Integrative genetic and epigenetic analysis uncovers regulatory mechanisms of autoimmune disease

## TL;DR

This study identifies regulatory DNA regions linked to autoimmune diseases and connects them to specific genes, offering new insights into disease mechanisms.

## Contribution

The study introduces a novel method to prioritize regulatory regions and their target genes across multiple autoimmune diseases.

## Key findings

- Regulatory potential was found in 44% of autoimmune disease risk loci.
- A single gene was prioritized in 79% of the identified regulatory regions.
- The approach generates testable hypotheses about molecular mechanisms of disease risk.

## Abstract

Genome-wide association studies in autoimmune and inflammatory diseases (AID) have uncovered hundreds of loci mediating risk1,2. These associations are preferentially located in non-coding DNA regions3,4 and in particular to tissue-specific Dnase I hypersensitivity sites (DHS)5,6. Whilst these analyses clearly demonstrate the overall enrichment of disease risk alleles on gene regulatory regions, they are not designed to identify individual regulatory regions mediating risk or the genes under their control, and thus uncover the specific molecular events driving disease risk. To do so we have departed from standard practice by identifying regulatory regions which replicate across samples, and connect them to the genes they control through robust re-analysis of public data. We find substantial evidence of regulatory potential in 132/301 (44%) risk loci across nine autoimmune and inflammatory diseases, and are able to prioritize a single gene in 104/132 (79%) of these. Thus, we are able to generate testable mechanistic hypotheses of the molecular changes that drive disease risk.