The use of the MOD score in linkage analysis
- Washington Univ. School of Medicine, St. Louis, MO (United States); and others
The detection of genes for complex diseases through linkage analysis has become feasible now that a dense genetic map is available. However, the best analytic approach to use is unclear when the mode of inheritance is unknown. In prior work, we simulated traits determined by 2, 4, or 6 loci with different degrees of heritability. Approaches which maximized the likelihood under a single-locus model (i.e. the wrong model) performed poorly both in terms of the expected lod score (ELOD) and an upward bias in the estimate of {theta}. MOD scores (lod scores maximized over genetic parameters) have been suggested by Risch (1984) and Clerget-Darpoux (1986) as a way to obviate difficulties due to unspecified ascertainment. The MOD score method is equivalent to maximizing the likelihood of the marker data conditional on all phenotypic data. In cases were segregation analysis under the wrong model would lead to {open_quotes}meaningless{close_quotes} parameter estimates, conditioning on the phenotypic information has intuitive appeal. We have modified the program ILINK of the LINKAGE package to allow maximization of the LOD score. The use of the MOD score gave the best results in the simulated oligogenic data sets. We estimated the three penetrances, and found the heterozygote penetrance to be close to the arithmetic mean of the homozygote penetrances, and reflected the underlying additive oligogenic model. It should be emphasized that without linkage data, there will be no information to estimate these parameters. We have derived analytic results in some special two-locus cases to indicate why the MOD worked in the simulation experiment. One useful feature of the MOD score statistic is that computations are done under the single-locus model, so, unlike the use of the two-trait locus model, the computations are feasible.
- OSTI ID:
- 133934
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0668
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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