To apply the dTDT on each SNP from COGA, we re-build the inferred pedigrees by extracting all trio combinations in which every child in a trio must be affected and at least one parent was genotyped on microsatellite markers. Because one family can have more than one affected child, the parents can be found in more than one trio. For instance, the family (FAM_ID 20059) as shown in Figure 3 has four affected children (#18, 1, 5 and 12, from left to right). Mother (#30) was genotyped on microsatellite markers. Therefore we have four trios from this family. In total, 893 trios from 323 families with 1,654 individuals in the LinkageMS EA group were extracted and used to build the trio-dosage pedigrees. 166 SNPs are found with p-values <10− 4. This is compared to 93 SNPs at the same level in Edenberg et al’s paper [79]. Several clusters of SNPs on chromosome 7, 8 and 22 have p-values ≤10− 5. However, further analysis with MH statistics does not yield consistent results with dTDT. This may be primarily due to the relatively small sample size used in dTDT and accuracy of the “–infer” program.
