Distilling pathophysiology from complex disease genetics.
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.
Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: aravinda@jhmi.edu.
Aravinda
A
Chakravarti
Andrew G
AG
Clark
Vamsi K
VK
Mootha
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D015984:Causality; D004194:Disease / Q000235:genetics*; D014644:Genetic Variation; D023281:Genomics / Q000379:methods*; D006801:Humans; D020412:Multifactorial Inheritance; D010641:Phenotype