For each of the two disease classifications, ALDX1 and ALDX2, we first performed linkage analysis over the whole genome, excluding the sex chromosome, using the methods of Li and Zhong [3], adjusting sex and smoking status as the covariates as well as the mean IBD test to analyze the microsatellite markers on each chromosome for linkage. The mean IBD test determines whether affected sib pairs share alleles at a specific marker more than the Mendelian expectation under no linkage. After the linkage evidence (p-value < 0.01) to some candidate genes is established, we further applied the association method [4] as well as the transmission/disequilibrium tests [7] to single-nucleotide polymorphism (SNP) markers within the peak regions.
