Scan statistics to scan markers for susceptibility genes

Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9615-7. doi: 10.1073/pnas.170179197.

Abstract

Scan statistics are applied to combine information on multiple contiguous genetic markers used in a genome screen for susceptibility loci. This information may be, for example, allele sharing proportions for sib pairs or logarithm of odds (lod) scores in general small families. We focus on a dichotomous outcome variable, for example, case and control individuals or affected-affected versus affected-unaffected siblings, and suitable single-marker statistics. A significant scan statistic based on the single-marker statistics represents evidence of the presence of a susceptibility gene. For a given length of the scan statistic, we assess its significance by Monte Carlo permutation tests. Comparing P values for varying lengths of scan statistics, we treat the smallest observed P value as our statistic of interest and determine its overall significance level. We applied this method to a genome screen with autism families. The result was informative and surprising: A susceptibility region was found (genome-wide significance level, P = 0.038), which is missed with conventional approaches.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Autistic Disorder / genetics*
  • Chromosome Mapping / methods*
  • Chromosome Mapping / statistics & numerical data*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genome, Human
  • Humans
  • Lod Score
  • Monte Carlo Method

Substances

  • Genetic Markers