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Two-locus Disease Models with Two Marker Loci: the Power of Affected-sib-pair Tests

Overview
Journal Am J Hum Genet
Publisher Cell Press
Specialty Genetics
Date 1994 Nov 1
PMID 7977340
Citations 16
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Abstract

Recently, Schork et al. found that two-trait-locus, two-marker-locus (parametric) linkage analysis can provide substantially more linkage information than can standard one-trait-locus, one-marker-locus methods. However, because of the increased burden of computation, Schork et al. do not expect that their approach will be applied in an initial genome scan. Further, the specification of a suitable two-locus segregation model can be crucial. Affected-sibpair tests are computationally simple and do not require an explicit specification of the disease model. In the past, however, these tests mainly have been applied to data with a single marker locus. Here, we consider sib-pair tests that make it possible to analyze simultaneously two marker loci. The power of these tests is investigated for different (epistatic and heterogeneous) two-trait-locus models, each trait locus being linked to one of the marker loci. We compare these tests both with the test that is optimal for a certain model and with the strategy that analyzes each marker locus separately. The results indicate that a straightforward extension of the well-known mean test for two marker loci can be much more powerful than single-marker-locus analysis and that is power is only slightly inferior to the power of the optimal test.

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References
1.
Neuman R, Rice J . Two-locus models of disease. Genet Epidemiol. 1992; 9(5):347-65. DOI: 10.1002/gepi.1370090506. View

2.
Durner M, Greenberg D, Hodge S . Inter- and intrafamilial heterogeneity: effective sampling strategies and comparison of analysis methods. Am J Hum Genet. 1992; 51(4):859-70. PMC: 1682807. View

3.
Schork N, Boehnke M, Terwilliger J, Ott J . Two-trait-locus linkage analysis: a powerful strategy for mapping complex genetic traits. Am J Hum Genet. 1993; 53(5):1127-36. PMC: 1682300. View

4.
Faraway J . Improved sib-pair linkage test for disease susceptibility loci. Genet Epidemiol. 1993; 10(4):225-33. DOI: 10.1002/gepi.1370100403. View

5.
Vieland V, Greenberg D, Hodge S . Adequacy of single-locus approximations for linkage analyses of oligogenic traits: extension to multigenerational pedigree structures. Hum Hered. 1993; 43(6):329-36. DOI: 10.1159/000154155. View