There are 20 scores estimating genetic factors in disease development

Recent years have seen a substantial rise of genomic data, projects, and associations with diseases. To cope with this vastness of data, scientists created at least 20 genetic scores connecting sequence variations with diseases.

All scores can be divided into three groups:

  • Assessment of mutations in essential genes influencing physiological functions (scores: Residual Variation Intolerance Score, Evolutionary inTolerance, De novo excesss, LoFtool, Substitution Intolerance Score, GERP++, pLI)
  • Detection of single copy genes (scores: Logarithm-of-odds, RECessive, Gene position in NETworks, dN/dS in chromosome X, Genome-wide HaploInsufficiency Score, Inheritance-mode Specific Pathogenicity Prioritization, DOMINO, HIpred)
  • Calculation of evolutionary pressure on genes (scores: Sel, Selection Inference using Poisson Random Effect, Gene-level Integrated Metric of negative Selection, Gene Damage Index, Poly-Phen-2)

Some of the scores are combined to provide an exhaustive evaluation of sequence variation in a disease context. For example, Mendelian Clinically Applicable Pathogenicity ties four scores to improve diagnosis precision.

Details about scores mentioned above are available under: “Gene-specific metrics to facilitate identification of disease genes for molecular diagnosis in patient genomes: a systematic review”, D. Alyousfi et al., 2018, doi:10.1093/bfgp/ely033.