Dosage Transmission Disequilibrium Test (dTDT) （剂量传输不平衡测试(dTDT)）.pdf

Dosage Transmission Disequilibrium Test (dTDT) for Linkage and Association Detection 1 1 1 1 1 Zhehao Zhang *, Jen-Chyong Wang , William Howells , Peng Lin , Arpana Agrawal , 2 3 4 1 1 1 Howard J. Edenberg , Jay A. Tischfield , Marc A. Schuckit , Laura J. Bierut , Alison Goate , John P. Rice * 1 Washington University School of Medicine, Department of Psychiatry, St. Louis, Missouri, United States of America, 2 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, 3 LSB 136, Rutgers University, Piscataway, New Jersey, United States of America, 4 Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America Abstract Both linkage and association studies have been successfully applied to identify disease susceptibility genes with genetic markers such as microsatellites and Single Nucleotide Polymorphisms (SNPs). As one of the traditional family-based studies, the Transmission/Disequilibrium Test (TDT) measures the over-transmission of an allele in a trio from its heterozygous parents to the affected offspring and can be potentially useful to identify genetic determinants for complex disorders. However, there is reduced information when complete trio information is unavailable. In this study, we developed a novel approach to ‘‘infer’’ the transmission of SNPs by combining both the linkage and association data, which uses microsatellite markers from families informative for linkage together with SNP markers from the offspring who are genotyped for both linkage and a G