title: A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia.
abstract: Inguinal 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.
authors.affiliation: Kaiser Permanente Northern California, Division of Research, Oakland, California 94612, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Jorgenson
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, California 94158, USA.|Institute for Human Genetics, UCSF, San Francisco, California 94158, USA.
authors.forename: Nadja
authors.initials: N
authors.lastname: Makki
authors.affiliation: Kaiser Permanente Northern California, Division of Research, Oakland, California 94612, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Lichtenstein Amid Hernia Clinic, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Chen
authors.affiliation: 23andMe Inc. 899 W. Evelyn Avenue, Mountain View, California 94041, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, California 94158, USA.|Institute for Human Genetics, UCSF, San Francisco, California 94158, USA.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Eckalbar
authors.affiliation: 23andMe Inc. 899 W. Evelyn Avenue, Mountain View, California 94041, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hinds
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, California 94158, USA.|Institute for Human Genetics, UCSF, San Francisco, California 94158, USA.
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
authors.affiliation: Kaiser Permanente Northern California, Division of Research, Oakland, California 94612, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Avins
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071096:ADAMTS Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015331:Cohort Studies; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006552:Hernia, Inguinal / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D051722:ADAM Proteins; D000071096:ADAMTS Proteins; D051792:Basic Helix-Loop-Helix Proteins; D016326:Extracellular Matrix Proteins; D025721:WT1 Proteins; C489923:EBF2 protein, human; C119630:EFEMP1 protein, human; C583751:WT1 protein, human; C121533:Adamts6 protein, human