Abstract
Resolution of the genetic components of complex disorders may require simultaneous analysis of the contribution of individual quantitative trait loci (QTLs) to multiple variables. A likelihood approach is used to illustrate how the complexities of multivariate data may be resolved with multipoint linkage analysis. Sibling pair data were simulated from a model in which two QTLs and trait-specific polygenic effects explained all the sibling resemblance within and between five variables. Multipoint linkage analysis was used to obtain individual pair probabilities of having zero, one, or two alleles identical by descent, and these probabilities were applied in a weighted maximum-likelihood fit function. The results were compared with those obtained using conventional linear structural equation modeling to estimate the contribution of latent genetic factors to the genetic covariance in the multiple measures. Both analyses were conducted using the Mx package. Relatively poor agreement was found between genetic factors defined in purely statistical terms by varimax rotation of the first two factors of the genetic covariance matrix and the structure obtained by fitting a model jointly to the phenotypic and the multipoint linkage data.
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References
Carey, G. (1986). A general multivariate approach to linear modelling in human genetics.Am. J. Hum. Genet. 39:775–786.
Eaves, L. J., Silberg J. L., Hewitt, J. K., Rutter, M., Meyet, J. M., Neale, M. C., and Pickles, A. (1993). Analyzing twin resemblance in multisymptom data: Genetic applications of latent class model for symptoms of conduct disorder in juvenile boys.Behav. Genet. 23:5–19.
Fulker, D. W. (1988). Genetic and cultural transmission in human behavior. In Weir, B. S., Eisen, E. J., Goodman, M., and Namkoong, G. (eds.),Proceedings of the Second International Conference on Quantitative Genetics, Sinauer Associates, Sunderland, MA.
Fulker, D. W., Cherny, S. S., and Cardon, L. R. (1995). Multipoint interval mapping of quantitative trait loci, using sib pairs.Am. J. Hum. Genet. 56:1224–1233.
Harman, H. H. (1976).Modern Factor Analysis, University of Chicago Press, Chicago.
Haseman, J. K., and Elston, R. C. (1972). The investigation of linkage between a quantitative trait and a marker locus.Behav. Genet. 2:3–19.
Hendrickson, A. E., and White, P. O. (1964). Promax; A quick method for rotation to oblique simple structure.Br. J. Stat. Psychol. 17:65–70.
Kaiser, H. F. (1958). The varimax criterion for analytical rotation in factor analysis.Psychometrika 23:187–200.
Kruglyak, L., and Lander, E. S. (1995). Complete multipoint sib-pair analysis of qualitative and quantitative traits.Am. J. Hum. Genet. 57:439–454.
Lander, E. S., and Botstein, D. (1989). Mapping mendelian factors underlying quantitative traits using RFLP linkage maps.Genetics 121:185–199.
Lander, E. S., and Green, P. (1986). Construction of multilocus genetic maps in humans.Proc. Natl. Acad. Sci. USA 84:2363–2367.
Little, R. J. A., and Rubin, D. B. (1987).Statistical Analysis with Missing Data, Wiley and Son, New York.
Martin, N. G., and Eaves, L. J. (1977). The genetical analysis of covariance structure.Heredity 38:79–95.
Neale, M. C. (1995).Mx: Statistical Modeling, 3rd ed., Box 710, Department of Psychiatry, MCV, Richmond, VA 23298.
Neale, M. C., and Cardon, L. R. (1992).Methodology for Genetic Studies of Twins and Families, Kluwer Academic, Dordrecht.
Risch, N., and Zhang, H. (1995). Extreme discordant sib pairs for mapping quantitative trait loci in humans.Science 268:1584–1589.
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Eaves, L.J., Neale, M.C. & Maes, H. Multivariate multipoint linkage analysis of quantitative trait loci. Behav Genet 26, 519–525 (1996). https://doi.org/10.1007/BF02359757
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DOI: https://doi.org/10.1007/BF02359757