Identification of fifty-seven novel loci for abdominal wall hernia development and their biological and clinical implications: results from the UK Biobank

Purpose Familial aggregation is known for both hernia development and recurrence. To date, only one genome-wide association study (GWAS) limited to inguinal hernia has been reported that identified four risk-associated loci. We aim to investigate polygenic architecture of abdominal wall hernia development and recurrence. Methods A GWAS was performed in 367,394 subjects from the UK Biobank to investigate the polygenic architecture of abdominal wall hernia subtypes (inguinal, femoral, umbilical, ventral) and identify specific single nucleotide polymorphisms (SNPs) that are associated with their risk. Expression quantitative trait loci (eQTL) analysis was performed to identify genes whose expression levels are associated with these SNPs. A genetic risk score (GRS) was used to assess the cumulative effect of multiple independent risk-associated SNPs on hernia development and recurrence in independent subjects ( n = 82,064). Results Heritability ( h 2 ) was 0.12, 0.06, 0.16, and 0.07 for inguinal, femoral, umbilical, and ventral hernias, respectively. A high-level of genetic correlation ( r g ) was found among these subtypes of hernia. We confirmed the aforementioned four loci and identified 57 novel loci ( P