Using affected sibling pairs to distinguish the direct effect of a susceptibility gene and the indirect effect of linkage disequilibrium.
A positive result for a transmission/disequilibrium test (TDT) can occur for two reasons: a) the allele itself is a cause of disease predisposition (direct effect); or b) the allele is in linkage disequilibrium with a disease-causing gene (indirect effect). A test was proposed based on affected sibling pairs (ASPs) to distinguish between the two. Simulation showed that the test has the correct type I error rate and favourable power (power >50% for 50 ASPs; >75% for 100 ASPs; >85% for 150 ASPs). Making this distinction is important for setting the direction for subsequent studies following a positive TDT result.
Lee
W-C
WC
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taiwan. wenchung@ha.mc.ntu.edu.tw
D000483:Alleles; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D015233:Models, Statistical; D013223:Statistics as Topic / Q000379:methods