Haplotype-based score test for linkage in nuclear families

Background: To look for genetic linkage between angiotensin-I converting enzyme(ACE) gene and hypertension in a Korean adolescent cohort, we developed a powerful test using the covariances between marginal differences and their variances in a transmission/non-transmission table. Results: We estimated haplotype frequencies using the parental and affected offspring's genotypes and then constructed a transmission/non-transmission table for the parental haplotypes transmitted to the offspring. We then proposed a test for checking the marginal homogeneity in the table. Because the cells in the table were dependent due to the uncertainty of the parental haplotypes, we adopted a randomization procedure to estimate the significance of the observed test statistic. Simulations show that our test performs well on a nominal level and has a monotone power, which increases as the relative risk increases. With our test, there was no evidence of genetic linkage between the ACE gene and hypertens...

• Type: Journal
• Year: 2007
• Where: BMCBI
• Authors: Chung Mo Nam, Dae Ryong Kang, Jinheum Kim
• Keywords: BMCBI 2007, Genetic Linkage, Haplotypes, Korean Adolescent Cohort