Scan statistics to scan markers for susceptibility genes.

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.