Email updates

Keep up to date with the latest news and content from BMC Bioinformatics and BioMed Central.

Open Access Methodology article

Haplotype-based score test for linkage in nuclear families

Chung Mo Nam1, Dae Ryong Kang1 and Jinheum Kim2*

Author Affiliations

1 Department of Preventive Medicine and Public Health, Yonsei University College of Medicine, Seoul, South Korea

2 Department of Applied Statistics, University of Suwon, Suwon, South Korea

For all author emails, please log on.

BMC Bioinformatics 2007, 8:277  doi:10.1186/1471-2105-8-277

Published: 1 August 2007



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.


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.


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.