Distilling pathophysiology from complex disease genetics

Cell. 2013 Sep 26;155(1):21-6. doi: 10.1016/j.cell.2013.09.001.


Technologies for genome-wide sequence interrogation have dramatically improved our ability to identify loci associated with complex human disease. However, a chasm remains between correlations and causality that stems, in part, from a limiting theoretical framework derived from Mendelian genetics and an incomplete understanding of disease physiology. Here we propose a set of criteria, akin to Koch's postulates for infectious disease, for assigning causality between genetic variants and human disease phenotypes.

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Causality
  • Disease / genetics*
  • Genetic Variation
  • Genomics / methods*
  • Humans
  • Multifactorial Inheritance
  • Phenotype*