Haplotype-based score test for linkage in nuclear families

<p>Abstract</p> <p>Background</p> <p>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 tr...

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Bibliographic Details
Main Authors: Kang Dae Ryong, Nam Chung Mo, Kim Jinheum
Format: Article
Language:English
Published: BMC 2007-08-01
Series:BMC Bioinformatics
Online Access:http://www.biomedcentral.com/1471-2105/8/277
Description
Summary:<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 hypertension in the Korean adolescent cohort.</p> <p>Conclusion</p> <p>We developed a score test for linkage and used simulations to demonstrate that our test performs well at a nominal level. Under some situations where the diversity of haplotypes is low, the proposed test gained a little power over the method based on only variances between marginal differences in a transmission/non-transmission table.</p>
ISSN:1471-2105