Using Full Genomic Information to Predict Disease: Breaking Down the Barriers Between Complex and Mendelian Diseases

Annu Rev Genomics Hum Genet. 2018 Aug 31:19:289-301. doi: 10.1146/annurev-genom-083117-021136. Epub 2018 Apr 11.

Abstract

While sequence-based genetic tests have long been available for specific loci, especially for Mendelian disease, the rapidly falling costs of genome-wide genotyping arrays, whole-exome sequencing, and whole-genome sequencing are moving us toward a future where full genomic information might inform the prognosis and treatment of a variety of diseases, including complex disease. Similarly, the availability of large populations with full genomic information has enabled new insights about the etiology and genetic architecture of complex disease. Insights from the latest generation of genomic studies suggest that our categorization of diseases as complex may conceal a wide spectrum of genetic architectures and causal mechanisms that ranges from Mendelian forms of complex disease to complex regulatory structures underlying Mendelian disease. Here, we review these insights, along with advances in the prediction of disease risk and outcomes from full genomic information.

Keywords: complex disease; disease prediction; genetic architecture; polygenic risk score.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Exome Sequencing
  • Genetic Diseases, Inborn / complications
  • Genetic Diseases, Inborn / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans