Researchers profiled epigenomic variation across hundreds of human tissue samples to understand how noncoding genetic variants influence complex diseases. By mapping H3K27ac histone marks in the brain, heart, muscle, and lung, the study identified over 280,000 active regulatory elements and linked them to specific biological contexts like sex and tissue type. The authors introduced haQTLs to reveal how genetic differences drive changes in these regulatory regions, providing a clearer map of the "circuits" between DNA variants and target genes. This data helps explain the molecular mechanisms behind conditions like schizophrenia by pinpointing which tissues and regulatory elements are impacted by disease-associated mutations. Finally, the study developed gLink scores, a new computational tool that uses genetic evidence to more accurately predict which genes are controlled by specific enhancers. Overall, this work expands the GTEx resource to bridge the gap between noncoding genetic sequences and the actual biological drivers of human traits.

References:

• Hou L, Xiong X, Park Y, et al. Multitissue H3K27ac profiling of GTEx samples links epigenomic variation to disease[J]. Nature Genetics, 2023, 55(10): 1665-1676.