Scan statistics to scan markers for susceptibility genes

Scan statistics are applied to combine information on multiple contiguous g enetic markers used in a genome screen for susceptibility loci. This inform ation may be, for example, allele sharing proportions for sib pairs or loga rithm of odds (lod) scores in general small families. We focus on a dichoto mous outcome variable, for example, case and control individuals or affecte d-affected versus affected-unaffected siblings, and suitable single-marker statistics. A significant scan statistic based on the single-marker statist ics represents evidence of the presence of a susceptibility gene. For a giv en length of the scan statistic, we assess its significance by Monte Carlo permutation tests. Comparing P values for varying lengths of scan statistic s, we treat the smallest observed P value as our statistic of interest and determine its overall significance level. We applied this method to a genom e 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.