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.
Laboratory of Statistical Genetics, Rockefeller University, New York, NY 10021, USA.
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J
Hoh
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J
Ott
D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D009010:Monte Carlo Method
D005819:Genetic Markers