Phenome‐wide association studies: a new method for functional genomics in humans

• Published in: The Journal of physiology Vol. 595; no. 12; pp. 4109 - 4115
• Main Author: Roden, Dan M.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 15.06.2017; John Wiley and Sons Inc
• Subjects: Animals; biobanks; Deoxyribonucleic acid; DNA; electronic health records; Electronic medical records; Genome-Wide Association Study - methods; genomics; Genomics - methods; GWAS; Harnessing Big Clinical Data for Basic Discovery; Humans; phenome; Phenotype; PheWAS; polygenic risk score; Polymorphism; Polymorphism, Single Nucleotide - genetics; Single-nucleotide polymorphism; Topical Review; PheWAS; biobanks; phenome; GWAS; genomics; electronic health records; polygenic risk score
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/JP273122

In experimental physiological research, a common study design for examining the functional role of a gene or a genetic variant is to introduce that genetic variant into a model organism (such as yeast or mouse) and then to search for phenotypic consequences. The development of DNA biobanks linked to dense phenotypic information enables such an experiment to be applied to human subjects in the form of a phenome‐wide association study (PheWAS). The PheWAS paradigm takes advantage of a curated medical phenome, often derived from electronic health records, to search for associations between ‘input functions’ and phenotypes in an unbiased fashion. The most commonly studied input function to date has been single nucleotide polymorphisms (SNPs), but other inputs, such as sets of SNPs or a disease or drug exposure, are now being explored to probe the genetic and phenotypic architecture of human traits. Potential outcomes of these approaches include defining subsets of complex diseases (that can then be targeted by specific therapies) and drug repurposing. The electronic health record (EHR) – a new ‘model organism’ to study human physiology.