SNPs Associated with Colorectal Cancer at 15q13.3 Affect Risk Enhancers That Modulate GREM1 Gene Expression

Overview

Journal Hum Mutat

Specialty Genetics

Date 2021 Jan 21

PMID 33476087

Citations 8

Authors

Barbara K Fortini

Stephanie Tring

Matthew A Devall

Mourad Wagdy Ali

Sarah J Plummer

Graham Casey

Affiliations

Soon will be listed here.

Abstract

Several genome wide association studies of colorectal cancer (CRC) have identified single nucleotide polymorphisms (SNPs) on chromosome 15q13.3 associated with CRC risk. To identify functional variant(s) underlying this association, we investigated SNPs in linkage disequilibrium with the risk-associated SNP rs4779584 that overlapped regulatory regions/enhancer elements characterized in colon-related tissues and cells. We identified several SNP-containing regulatory regions that exhibited enhancer activity in vitro, including one SNP (rs1406389) that correlated with allele-specific effects on enhancer activity. Deletion of either this enhancer or another enhancer that had previously been reported in this region correlated with decreased expression of GREM1 following CRISPR/Cas9 genome editing. That GREM1 is one target of these enhancers was further supported by an expression quantitative trait loci correlation between rs1406389 and GREM1 expression in the transverse but not sigmoid colon in the Genotype-Tissue Expression dataset. Taken together, we conclude that the 15q13.3 region contains at least two functional variants that map to distinct enhancers and impact CRC risk through modulation of GREM1 expression.

Citing Articles

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