A genotype-first approach to defining the subtypes of a complex disease

Cell. 2014 Feb 27;156(5):872-7. doi: 10.1016/j.cell.2014.02.002.


Medical genetics typically entails the detailed characterization of a patient's phenotypes followed by genotyping to discover the responsible gene or mutation. Here, we propose that the systematic discovery of genetic variants associated with complex diseases such as autism are progressing to a point where a reverse strategy may be fruitful in assigning the pathogenic effects of many different genes and in determining whether particular genotypes manifest as clinically recognizable phenotypes. This "genotype-first" approach for complex disease necessitates the development of large, highly integrated networks of researchers, clinicians, and patient families, with the promise of improved therapies for subsets of patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder / classification
  • Autistic Disorder / diagnosis
  • Autistic Disorder / genetics*
  • Community Networks
  • Exome
  • Genetic Heterogeneity*
  • Genotype*
  • Humans
  • Mutation
  • Phenotype