Haplotype-based score test for linkage in nuclear families

Chung Mo Nam,Dae Ryong Kang,Jinheum Kim

doi:10.1186/1471-2105-8-277

Chung Mo Nam, Dae Ryong Kang + Show 1 more

Open Access

https://doi.org/10.1186/1471-2105-8-277

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Journal: BMC bioinformatics	Publication Date: Aug 1, 2007
Citations: 16	License type: cc-by

Affiliation: Yonsei University, University of Suwon

Abstract

BackgroundTo 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.ResultsWe 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.ConclusionWe 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.

Highlights

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
Based on various situations incorporated in the simulations, we have shown that both our proposed test and Zhao et al's test are robust to population admixture
We found that our proposed test as well as Zhao et al's test is robust to population admixture

Summary

Introduction

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. The likelihood ratio test, which is based on the difference between the sum of the log-likelihoods of the case and control groups and the log-likelihood of the combined data, is usually used for case-control association studies [4], while the TDT is used for linkage and/or association studies in nuclear families. The latter compares the frequency of transmitted parental haplotypes with that of non-transmitted parental haplotypes to an affected offspring. Zhao et al [8] extended Spielman and Ewens' method [9] to test for marginal homogeneity in the transmission and non-

Results

Discussion

Conclusion