A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia

• DOI: 10.1038/ncomms10130
• Publication Date: 2015-12-21T10:24:39Z
• Authors: Eric Jorgenson; Nadja Makki; Ling Shen; David C. Chen; Chao Tian; Walter L. Eckalbar; David Hinds; Nadav Ahituv; Andrew Avins
• Keywords: Adult; Male; Hernia; 610; Hernia, Inguinal; Article; Cohort Studies; Mice; 03 medical and health sciences; ADAMTS Proteins; Clinical Research; 80 and over; Genetics; Basic Helix-Loop-Helix Transcription Factors; 2.1 Biological and endogenous factors; Animals; Humans; Genetic Predisposition to Disease; Aetiology; WT1 Proteins; Aged; Aged, 80 and over; Extracellular Matrix Proteins; 0303 health sciences; Human Genome; 600; Middle Aged; 3. Good health; ADAM Proteins; Inguinal; Female; Digestive Diseases; Biotechnology; Genome-Wide Association Study

AbstractInguinal hernia repair is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop inguinal hernias. We perform a genome-wide association analysis of surgically confirmed inguinal hernias in 72,805 subjects (5,295 cases and 67,510 controls) and confirm top associations in an independent cohort of 92,444 subjects with self-reported hernia repair surgeries (9,701 cases and 82,743 controls). We identify four novel inguinal hernia susceptibility loci in the regions of EFEMP1, WT1, EBF2 and ADAMTS6. Moreover, we observe expression of all four genes in mouse connective tissue and network analyses show an important role for two of these genes (EFEMP1 and WT1) in connective tissue maintenance/homoeostasis. Our findings provide insight into the aetiology of hernia development and highlight genetic pathways for studies of hernia development and its treatment.