Biological findings from the PheWAS catalog: focus on connective tissue-related disorders (pelvic floor dysfunction, abdominal hernia, varicose veins and hemorrhoids)

Hum Genet. 2016 Jul;135(7):779-95. doi: 10.1007/s00439-016-1672-8. Epub 2016 Apr 28.


Pelvic floor dysfunction, specifically genital prolapse (GP) and stress urinary inconsistency (SUI) presumably co-occur with other connective tissue disorders such as hernia, hemorrhoids, and varicose veins. Observations on non-random coexistence of these disorders have never been summarized in a meta-analysis. The performed meta-analysis demonstrated that varicose veins and hernia are associated with GP. Disease connections on the molecular level may be partially based on shared genetic susceptibility. A unique opportunity to estimate shared genetic susceptibility to disorders is provided by a PheWAS (phenome-wide association study) designed to utilize GWAS data concurrently to many phenotypes. We searched the PheWAS Catalog, which includes the results of the PheWAS study with P value < 0.05, for genes associated with GP, SUI, abdominal hernia, varicose veins and hemorrhoids. We found pronounced signals for the associations of the SLC2A9 gene with SUI (P = 6.0e-05) and the MYH9 gene with varicose veins of lower extremity (P = 0.0001) and hemorrhoids (P = 0.0007). The comparison of the PheWAS Catalog and the NHGRI Catalog data revealed enrichment of genes associated with bone mineral density in GP and with activated partial thromboplastin time in varicose veins of lower extremity. In cross-phenotype associations, genes responsible for peripheral nerve functions seem to predominate. This study not only established novel biologically plausible associations that may warrant further studies but also exemplified an effective use of the PheWAS Catalog data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Connective Tissue / pathology
  • Databases, Factual
  • Genetic Predisposition to Disease
  • Hemorrhoids / epidemiology
  • Hemorrhoids / genetics*
  • Hemorrhoids / physiopathology
  • Hernia, Abdominal / epidemiology
  • Hernia, Abdominal / genetics*
  • Hernia, Abdominal / physiopathology
  • Humans
  • Pelvic Floor Disorders / epidemiology
  • Pelvic Floor Disorders / genetics*
  • Pelvic Floor Disorders / physiopathology
  • Phenotype
  • Risk Factors
  • Varicose Veins / epidemiology
  • Varicose Veins / genetics*
  • Varicose Veins / physiopathology