Family-Based Association Analysis with Tightly Linked MarkersKnapp M. · Becker T.
Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
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Refining genomic regions which have been identified by linkage analysis to contain a disease susceptibility locus has proven to be a challenging task. Detecting association between the disease and a genetic marker can significantly narrow down the candidate region. Since an adequate sample of families is already available from the genome scan, family-based association tests may be used to search for association. The use of haplotypes consisting of tightly linked markers can be more powerful for detecting association than the use of individual markers. An extension of the transmission/disequilibrium test to allow the simultaneous analysis of more than one marker locus is complicated by ambiguity of phase in some families of the sample. The present paper shows that a recently proposed method for the analysis of nuclear families with a single affected child can be viewed as a special application of a more general principle. This observation justifies several modifications, potentially increasing the power, as well as an extension of the method to allow the analysis of general nuclear families. Finally, the problem of missing parental genotypes is discussed.
© 2003 S. Karger AG, Basel
- Zhao H: Family-based association studies. Stat Methods Med Res 2000;9:563–587.
Spielman RS, McGinnis RE, Ewens WJ: Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM) Am J Hum Genet 1993;52:506–516.
- Martin ER, Kaplan NL, Weir BS: Tests for linkage and association in nuclear families. Am J Hum Genet 1997;61:439–448.
Müller-Myhsok B, Abel L: Genetic analysis of complex diseases. Science 1997;275:1328–1329.
- Abel L, Müller-Myhsok B: Maximum-likelihood expression of the transmission/disequilibrium test and power considerations. Am J Hum Genet 1998;63:664–667.
- Michalatos-Beloin S, Tishkoff SA, Bentley KL, Kidd KK, Ruano G: Molecular haplotyping of genetic markers 10 kb apart by allele-specific long-range PCR. Nucleic Acids Res 1996;24:4841–4843.
- Zhao H, Zhang S, Merikangas KR, Trixler M, Wildenauer DB, Sun F, Kidd KK: Transmission/disequilibrium tests using multiple tightly linked markers. Am J Hum Genet 2000;67:936–946.
- Spielman RS, Ewens WJ: The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet 1996;59:983–989.
- Becker T, Knapp M: Efficiency of haplotype frequency estimation when nuclear family information is included. Hum Hered 2002;54:45–53.
- Schaid DJ: Relative efficiency of ambiguous vs. directly measured haplotype frequencies. Genet Epidemiol 2002;23:426–443.
Sham PC, Curtis D: An extended transmission/disequilibrium test (TDT) for multi-allele marker loci. Ann Hum Genet 1995;59:323–336.
- Schaid DJ: General score tests for associations of genetic markers with disease using cases and their parents. Genet Epidemiol 1996;13:423–449.
Morris AP, Curnow RN, Whittaker JC: Randomization tests of disease-marker associations. Ann Hum Genet 1997;61:49–60.
- Clayton DG: A generalization of the transmission/disequilibrium test for uncertain haplotype transmission. Am J Hum Genet 1999;65:1170–1177.
- Dudbridge F, Koeleman BPC, Todd JA, Clayton DG: Unbiased application of the transmission/disequilibrium test to multilocus haplotypes. Am J Hum Genet 2000;66:2009–2012.
- Allen AS, Rathouz PJ, Satten GA: Informative missingness in genetic association studies: case-parent designs. Am J Hum Genet 2003;72:671–680.
Rabinowitz D: Adjusting for population heterogeneity and misspecified haplotype frequencies when testing nonparametric null hypotheses in statistical genetics. J Am Stat Assoc 2002;97:742–751.
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