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. 2003 Sep;73(3):566-79.
doi: 10.1086/378205. Epub 2003 Aug 15.

Transmission/disequilibrium test based on haplotype sharing for tightly linked markers

Shuanglin Zhang  1 , Qiuying Sha, Huann-Sheng Chen, Jianping Dong, Renfang Jiang
Affiliations

Transmission/disequilibrium test based on haplotype sharing for tightly linked markers

Shuanglin Zhang et al. Am J Hum Genet. 2003 Sep.

Abstract

Studies using haplotypes of multiple tightly linked markers are more informative than those using a single marker. However, studies based on multimarker haplotypes have some difficulties. First, if we consider each haplotype as an allele and use the conventional single-marker transmission/disequilibrium test (TDT), then the rapid increase in the degrees of freedom with an increasing number of markers means that the statistical power of the conventional tests will be low. Second, the parental haplotypes cannot always be unambiguously reconstructed. In the present article, we propose a haplotype-sharing TDT (HS-TDT) for linkage or association between a disease-susceptibility locus and a chromosome region in which several tightly linked markers have been typed. This method is applicable to both quantitative traits and qualitative traits. It is applicable to any size of nuclear family, with or without ambiguous phase information, and it is applicable to any number of alleles at each of the markers. The degrees of freedom (in a broad sense) of the test increase linearly as the number of markers considered increases but do not increase as the number of alleles at the markers increases. Our simulation results show that the HS-TDT has the correct type I error rate in structured populations and that, in most cases, the power of HS-TDT is higher than the power of the existing single-marker TDTs and haplotype-based TDTs.

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Figures

Figure  1
Figure  1
Calculation of the similarity between two haplotypes around a specific marker. The similarity is taken as the length of the region shared IBS around this marker.
Figure  2
Figure  2
Power comparison of the six tests for a qualitative trait. The sample size is 200 families with one affected child in each family.
Figure  3
Figure  3
Power comparison of the three tests for a quantitative trait—with two children in each family. The sample size is 200 families.
Figure  4
Figure  4
Power comparison of the three tests for a quantitative trait—with heritability fixed at 6%. The sample size is 200 families.
See this image and copyright information in PMC

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References

    1. Allison DB (1997) Transmission-disequilibrium tests for quantitative traits. Am J Hum Genet 60:676–690 (erratum 60:1571) - PMC - PubMed
    1. Bickeboller H, Clerget-Darpoux F (1995) Statistical properties of the allelic and genotypic transmission/disequilibrium test for multiallelic markers. Genet Epidemiol 12:865–870 - PubMed
    1. Boehnke M, Langefeld CD (1998) Genetic association mapping based on discordant sib pairs: the discordant-alleles test. Am J Hum Genet 62:950–961 - PMC - PubMed
    1. Bourgain C, Génin E, Holopainen P, Mustalahti K, Mäki M, Partanen J, Clerget-Darpoux F (2001) Use of closely related affected individuals for the genetic study of complex disease in founder populations. Am J Hum Genet 68:154–159 - PMC - PubMed
    1. Bourgain C, Genin E, Ober C, Clerget-Darpoux F (2002) Missing data in haplotype analysis: a study on the MILC method. Ann Hum Genet 66:99–108 - PubMed

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