Researchers from Oxford and Estonia have found further evidence that a person’s genetic make-up and height can influence whether they will develop carpal tunnel syndrome (CTS).
In the first ever genome-wide association study of CTS, published today in Nature Communications, the researchers from the University of Oxford and the Estonian Genome Center revealed 16 specific locations in chromosomes associated with the condition, and a link between short stature and the risk of developing the condition.
The study, supported by the NIHR Oxford Biomedical Research Centre and the Medical Research Council, used data from over 12,000 CTS patients from the UK Biobank.
CTS is a common and disabling condition of the hand, caused by pressure on a nerve in the wrist. It can be very painful and causes tingling, numbness and weakness of the hand, sometimes leading to severe loss of function.
Approximately one in 20 people in the UK will develop CTS at some point in their life, and CTS surgery is the most commonly performed operation by hand surgeons worldwide. With the number of operations for CTS expected to double between 2011 and 2030, the condition poses a considerable socioeconomic burden.
Despite being so common, the reason why certain people develop CTS is poorly understood, and even less is known about how genes determine who is more likely to develop the condition.
Lead author Akira Wiberg, of the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), said: “Many people have heard of carpal tunnel syndrome, and it is popularly portrayed as a disease associated with hand overuse.
“While there is evidence that certain occupational factors can increase an individual’s risk of developing CTS, most people, including many doctors, are probably unaware that genetic risk factors are thought to be the most important determinants of who goes on to develop the disease. This study adds considerable weight to the genetic side of the story.”
The researchers used the BioBank information to perform a genome-wide association study (GWAS), which can show the regions in the human genome where variants in the DNA sequence contribute to disease risk. Sixteen such regions were identified in this study, leading to the identification of numerous candidate genes that are likely to contribute to the development of CTS.
Several of these genes are known to be important in determining human height, and this study not only demonstrated that being shorter increases an individual’s risk of developing CTS, but provided the first ever explanation as to why people with CTS tend to be, on average, just under an inch shorter than those without CTS.
Using human tissues taken at the time of carpal tunnel surgery from a group of CTS patients in Oxford, the researchers showed that the genes discovered in the GWAS are highly expressed in the connective tissues around the median nerve in the carpal tunnel, suggesting that genetic variants alter these tissues to increase CTS risk.
The identification of these genes has not only advanced the understanding of the biology of CTS, but has opened up several new avenues of research, including how to use genetics to predict individuals who are at increased risk of developing CTS.