Clinical utility of sequence-based genotype compared with that derivable from genotyping arrays

J Am Med Inform Assoc. 2012 Jun;19(e1):e21-7. doi: 10.1136/amiajnl-2011-000737.


Objective: We investigated the common-disease relevant information obtained from sequencing compared with that reported from genotyping arrays.

Materials and methods: Using 187 publicly available individual human genomes, we constructed genomic disease risk summaries based on 55 common diseases with reported gene-disease associations in the research literature using two different risk models, one based on the product of likelihood ratios and the other on the allelic variant with the maximum associated disease risk. We also constructed risk profiles based on the single nucleotide polymorphisms (SNPs) of these individuals that could be measured or imputed from two common genotyping array platforms.

Results: We show that the model risk predictions derived from sequencing differ substantially from those obtained from the SNPs measured on commercially available genotyping arrays for several different non-monogenic diseases, although high density genotyping arrays give identical results for many diseases.

Conclusions: Our approach may be used to compare the ability of different platforms to probe known genetic risks disease by disease.

Publication types

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

MeSH terms

  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing / methods
  • Genotype
  • Humans
  • Likelihood Functions
  • Oligonucleotide Array Sequence Analysis*
  • Sequence Analysis, DNA*