Identifying Genetic Variants Associated with Chromatin Looping and Genome Function

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Sep 17

PMID 39289357

Authors

Sourya Bhattacharyya

Ferhat Ay

Affiliations

Soon will be listed here.

Abstract

Here we present a comprehensive HiChIP dataset on naïve CD4 T cells (nCD4) from 30 donors and identify QTLs that associate with genotype-dependent and/or allele-specific variation of HiChIP contacts defining loops between active regulatory regions (iQTLs). We observe a substantial overlap between iQTLs and previously defined eQTLs and histone QTLs, and an enrichment for fine-mapped QTLs and GWAS variants. Furthermore, we describe a distinct subset of nCD4 iQTLs, for which the significant variation of chromatin contacts in nCD4 are translated into significant eQTL trends in CD4 T cell memory subsets. Finally, we define connectivity-QTLs as iQTLs that are significantly associated with concordant genotype-dependent changes in chromatin contacts over a broad genomic region (e.g., GWAS SNP in the RNASET2 locus). Our results demonstrate the importance of chromatin contacts as a complementary modality for QTL mapping and their power in identifying previously uncharacterized QTLs linked to cell-specific gene expression and connectivity.

Citing Articles

Genetic coupling of enhancer activity and connectivity in gene expression control.

Ray-Jones H, Sung C, Chan L, Haglund A, Artemov P, Della Rosa M Nat Commun. 2025; 16(1):970.

PMID: 39870618 PMC: 11772589. DOI: 10.1038/s41467-025-55900-3.

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