Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-27T22:01:14.305Z Has data issue: false hasContentIssue false

The maximum of a function of a Markov chain and application to linkage analysis

Published online by Cambridge University Press:  01 July 2016

I-Ping Tu*
Affiliation:
Stanford University
David Siegmund*
Affiliation:
Stanford University
*
Postal address: Department of Health Research and Policy, Stanford University, Stanford, CA 94305, USA.
∗∗ Postal address: Department of Statistics, Stanford University, 390 Serra Mall, Stanford, CA 94305-4065, USA. Email address: dos@stat.stanford.edu

Abstract

One method of linkage analysis in humans is based on identity-by-descent of pairs of relatives who share a phenotype of interest (for example, a particular disease). We replace the convenient assumption of continuous specification of regions of identity by descent by the more realistic, although still artificially simple, assumption of data from a discrete set of equally spaced infinitely polymorphic markers. We generalize the continuous time Markov chain analysis of Feingold (1993b) and compare the accuracy of the new approximation with that of the simpler Gaussian approximation of Feingold, Brown and Siegmund (1993) under a variety of assumptions about the composition of the pedigrees to be studied. We also suggest a perturbation of the Gaussian approximation as a compromise to achieve reasonable accuracy with minimal computational effort.

MSC classification

Type
General Applied Probability
Copyright
Copyright © Applied Probability Trust 1999 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aldous, D. (1989). Probability Approximation via the Poisson Clumping Heuristic. Springer, New York.CrossRefGoogle Scholar
Davies, J. L., Kawaguchi, Y, Bennett, S. T., Copeman, J. B., Cordell, H. J., Pritchard, L. E., Reed, P. W. et al. (1994). A genome-wide search for human type I diabetes susceptibility genes. Nature 371, 130136.CrossRefGoogle ScholarPubMed
Dupuis, J. (1994). Statistical problems associated with mapping complex and quantitative traits from genomic mismatch scanning data. , Stanford University, Stanford, CA.Google Scholar
Feingold, E. (1993a). Modeling a New Genetic Mapping Method. , Stanford University, Stanford, CA.Google Scholar
Feingold, E. (1993b). Markov processes for modeling and analyzing a new genetic mapping method. J. Appl. Prob. 30, 766779.CrossRefGoogle Scholar
Feingold, E. and Siegmund, D. (1997). Strategies for mapping hetrogeneous recessive traits by allele-sharing methods. Am. J. Hum. Genet. 60, 965978.Google Scholar
Feingold, E., Brown, P. O. and Siegmund, D. (1993). Gaussian models for genetic linkage analysis using complete high resolution maps of identity by descent. Am. J. Hum. Genet. 53, 234251.Google ScholarPubMed
Feller, W. (1972). An Introduction to Probability Theory and Its Applications, Vol. 2. Wiley, New York.Google Scholar
Gschwend, M., Levran, O., Kruglyak, L., Verlander, P. C., Shen, S., Faure, S., Weissenbach, J., Altay, C., Lander, E. S., Auerbach, A. D., Botstein, D. (1996). A locus for Fanconi anemia on 16q determined by homozygosity mapping. Am. J. Hum. Genet. 59, 377384.Google ScholarPubMed
Kruglyak, L. and Lander, E. S. (1995). Complete multipoint sib pair analysis of qualitative and quantitative traits. Am. J. Hum. Genet. 57, 439454.Google ScholarPubMed
Lander, E. S. and Botstein, D. (1987). Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236, 15671570.CrossRefGoogle ScholarPubMed
Lander, E. S. and Schork, N. J. (1994). Genetic dissection of complex traits. Science 265, 20372048.CrossRefGoogle ScholarPubMed
Mahtani, M. M., Widen, E., Lehto, M., Thomas, J., McCarthy, M., Brayer, J., Bryant, B., Chan, G., Daly, M., Forsblom, C., Kanninen, T., Kirby, A., Kruglyak, L., Munnelly, K., Parkkonen, M., Reeve-Daly, M. P., Weaver, A., Brettin, T., Duyk, G., Lander, E. S. and Groop, L. C. (1996). Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families. Nature Genetics 14, 9094.CrossRefGoogle ScholarPubMed
Ott, J. (1991). Analysis of Human Genetic Linkage, revd edn. Johns Hopkins, Baltimore.Google Scholar
Rabinowitz, D. and Siegmund, D. (1997). The approximate distribution of the maximum of a smoothed Poisson random field. Statist. Sinica 7, 167180.Google Scholar
Risch, N. (1990a). Linkage strategies for genetically complex traits. I. Multilocus models.. 46, 222228.Google ScholarPubMed
Risch, N. (1990b). Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am. J. Hum. Genet. 46, 229241.Google ScholarPubMed
Siegmund, D. (1985). Sequential Analysis: Tests and Confidence Intervals. Springer, New York.CrossRefGoogle Scholar
Siegmund, D. (1988). Approximate tail probabilities for the maxima of some random fields. Ann. Prob. 16, 487501.CrossRefGoogle Scholar
Suarez, B. K., Rice, J. and Reich, T. (1978). The generalized sib pair IBD distribution: its use in the detection of linkage. Ann. Hum. Genet. 44, 8794.CrossRefGoogle Scholar
Teng, J. and Siegmund, D. (1997). Combining information within and between pedigrees for mapping complex traits. Am. J. Hum. Genet. 60, 979992.Google ScholarPubMed
Teng, J. and Siegmund, D. (1998). Multipoint linkage analysis using affected relative pairs and partially informative markers. Biometrics 54, 12471265.CrossRefGoogle ScholarPubMed
Wald, A. (1947). Sequential Analysis. Wiley, New York.Google Scholar
Whittemore, A. and Tu, I. (1998). Simple, robust linkage tests for affected sibs. Am. J. Hum. Genet. 62, 12281242.CrossRefGoogle ScholarPubMed
Woodroofe, M. (1976). Frequentist properties of Bayesian sequential tests. Biometrika 63, 101110.CrossRefGoogle Scholar
Woodroofe, M. (1979). Repeated likelihood ratio tests. Biometirka 66, 453463.CrossRefGoogle Scholar
Woodroofe, M. (1982). Nonlinear Renewal Theory in Sequential Analysis. SIAM, Philadelphia, PA.CrossRefGoogle Scholar