DIRC3-IGFBP5 is a shared genetic risk locus and therapeutic target for carpal tunnel syndrome and trigger finger

Patel, Benjamin, Kleeman, Sam, Neavin, Drew, Powell, Joseph, Baskozos, Georgios, Ng, Michael, Ahmed, Waheed-Ul-Rahman, Bennett, David, Schmid, Annina, Furniss, Dominic, Wiberg, Akira (October 2021) DIRC3-IGFBP5 is a shared genetic risk locus and therapeutic target for carpal tunnel syndrome and trigger finger. medRxiv. (Submitted)

PDF 10.1101.2021.10.07.21264697.pdf - Submitted Version Available under License Creative Commons Attribution Non-commercial. Download (3MB)

Abstract

Trigger finger (TF) and carpal tunnel syndrome (CTS) are two common non-traumatic hand disorders that frequently co-occur. By identifying TF and CTS cases in UK Biobank (UKB), we confirmed a highly significant phenotypic association between the diseases. To investigate the genetic basis for this association we performed a genome-wide association study (GWAS) including 2,908 TF cases and 436,579 European controls in UKB, identifying five independent loci. Colocalization with CTS summary statistics identified a co-localized locus at DIRC3 (lncRNA), which was replicated in FinnGen and fine-mapped to rs62175241. Single-cell and bulk eQTL analysis in fibroblasts from healthy donors (n=79) and tenosynovium samples from CTS patients (n=77) showed that the disease-protective rs62175241 allele was associated with increased DIRC3 and IGFBP5 expression. IGFBP5 is a secreted antagonist of IGF-1 signaling, and elevated IGF-1 levels were associated with CTS and TF in UKB, thereby implicating IGF-1 as a driver of both diseases.

Item Type:	Paper
CSHL Authors:	Kleeman, Sam
Communities:	CSHL labs > Janowitz lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	21 October 2021
Date Deposited:	22 Jul 2025 13:45
Last Modified:	22 Jul 2025 13:45
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41913

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