New insights into the genetic architecture of inguinal hernia

Abstract

Inguinal hernia occurs when the abdominal contents protrude though a weak point in the abdominal wall. More than one in three men and one in five women will develop hernias that require surgical repair [1,2]. In fact, hernia repair is the most common surgical procedure, with more than 20 million hernia repair surgeries performed globally per year. Many patients experience serious post-surgical complications, including chronic pain and hernia recurrence [3]. Delaying treatment carries the risk of bowel incarceration and is associated with a substantial risk of mortality [4,5]. Thus, inguinal hernia is a global public health issue, and there is a clear need for a better understanding of hernia etiology, new methods for early detection, and improved treatment options. Several risk factors underlying inguinal hernia development have been identified including male sex, older age, chronic obstructive pulmonary disease, lower body mass index, and family history [2]. Despite its prevalence, few genetic factors underlying inguinal hernia risk have been identified. A previous genome-wide association study (GWAS) identified four significant loci in populations of European descent [6], but similar work in non-European populations had not been carried out. In the current issue of EBioMedicine, Hikino and colleagues identifiy six novel inguinal hernia susceptibility loci and study the polygenic architecture of the disease by highlighting common and population-specific features in inguinal hernia. Specifically, they performed GWAS on subjects with inguinal hernias from the BioBank Japan (BBJ) with 1,983 cases and 172,507 controls, and identified a locus closest to the elastin gene (ELN) to be associated with inguinal hernia [6]. They followed up with a trans-ethnic meta-analysis including UK Biobank (UKBB) data that identified five additional novel loci: TGFB2, RNA5SP214/VGLL2, LOC646588, HMCN2, and ATP5F1CP1/CDKN3. Computational downstream analysis revealed highly shared polygenetic architectures across populations, as well as population-specific variants in the ELN locus in the BBJ and UKBB populations. Further analyses using data sets of putative regulatory