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 hypertension in the Korean adolescent cohort.


CONCLUSIONS
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.
Nam
Chung Mo
CM
Department of Applied Statistics, University of Suwon, Suwon, South Korea. cmnam@yumc.yonsei.ac.kr
Kang
Dae Ryong
DR
Kim
Jinheum
J
D000293:Adolescent; D015331:Cohort Studies; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007723:Korea; D008126:Lod Score; D009679:Nuclear Family; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D007703:Peptidyl-Dipeptidase A