Abstract
A population is composed of individuals who are heterogeneous in their susceptibility to death and disease. This heterogeneity is reflected in the age-specific incidence or mortality (hazard) function. This variation has typically been hidden—that is, not measured directly—and has generally been modeled in a purely empirical statistical way, because there is no theory in demography for the distribution of frailty. A substantial fraction of variation in frailty, however, has an underlying genetic basis, for which there is a formal theory. This theory, based on evolutionary biology and on the nature of mendelian transmission, provides prior constraints on the distribution of variation in the population as well as providing methods for identifying genes involved in many important diseases. The accumulating effects of environmental exposures with age are another major component of variation in frailty. In some important instances, this variation and its effect on the age-specific hazard function can also be understood in terms of cause-specific biological processes. These biological considerations may enable demographers to model frailty, and thus mortality, in a better way.
Similar content being viewed by others
References
Bishop, D. T., & Skolnick, M. H. (1984). “Genetic Epidemiology of Cancer in Utah Genealogies: A Prelude to the Molecular Genetics of Common Cancers.” Journal of Cell Physiology, 3 (suppl.), 63–77.
Bock, G., & Collins, G. M. (1987). Molecular Approaches to Human Polygenic Disease, CIBA Foundation Symposium, No. 130. Chichester, UK: Wiley.
Boerwinkle, E., & Sing, C. F. (1987). “The Use of Measured Genotype Information in the Analysis of Quantitative Phenotypes in Man. Ill: The Role of the Apolipoprotein E Polymorphism in Determining Levels, Variability, and Covariability of Cholesterol, Betalipoprotein, and Triglycerides in a Sample of Unrelated Individuals.” American Journal of Medical Genetics, 27, 567–582.
Boerwinkle, E., Visvikis, S., Welsh, D., Steinmetz, J., Hanash, S. M., & Sing, C. F. (1987). “The Use of Measured Genotype Information in the Analysis of Quantitative Phenotypes in Man. II: Simultaneous Estimation of the Frequencies and Effects of the Apolipoprotein E Polymorphism and Residual Polygenic Effects on Cholesterol, Betalipoprotein and Triglyceride Levels.” Annals of Human Genetics, 51, 211–226.
Bonney, G. E., Lathrop, G. M., & Lalouel, J.-M. (1988). “Combined Linkage and Segregation Analysis Using Regressive Models.” American Journal of Human Genetics, 43, 29–37.
Breslow, N. E., & Day, N. E. (1980). Statistical Methods in Cancer Research (Vol. 1): The Analysis of Case-Control Studies. Lyon, France: International Agency for Research on Cancer.
—, (1987). Statistical Methods in Cancer Research (Vol. 2): The Design and Analysis of Cohort Studies. Lyon, France: International Agency for Research on Cancer.
Cannon-Albright, L. A., Skolnick, M. H., Bishop, T., Lee, R. G., & Burt, R. W. (1988). “Common Inheritance of Susceptibility to Colonic Adenomatous Polyps and Associated Colorectal Cancers.” New England Journal of Medicine, 319, 533–537.
Chakraborty, R., Ferrell, R. E., Stern, M. P., Haffner, S. M., Hazuda, H. P., & Rosenthal, M. (1986). “Relationship of Prevalence of Non-insulin-dependent Diabetes Mellitus to Amerindian Admixture in the Mexican Americans of San Antonio, Texas.” Genetic Epidemiology, 3, 435–454.
Chakraborty, R., & Weiss, K. M. (1989). “Age-Specific Risks for Cancer as Determined by Multi-stage Models of Carcinogenesis.” In Statistics in Medicine, ed. T. Krishnan. Bombay, India: Himalaya Publishing House, pp. 64–91.
Cook, P. J., Doll, R., & Fellingham, S. A. (1969). “A Mathematical Model for the Age Distribution of Cancer in Man.” International Journal of Cancer, 4, 93–112.
Doll, R., & Peto, R. (1978). “Cigarette Smoking and Bronchial Carcinoma: Dose and Time Relationships Among Regular Smokers and Life-Long Non-smokers.” Journal of Epidemiology and Community Health, 32, 303–313.
— (1980). The Causes of Cancer. Oxford, UK: Oxford University Press.
Elandt-Johnson, R. C. (1971). Probability Models and Statistical Methods in Genetics. New York: Wiley.
Elston, R. C. (1981). “Segregation Analysis.” In Advances in Human Genetics (Vol. 11), eds. H. Harris & K. Hirschhorn. New York: Plenum, pp. 63–120.
— (1986). “Modern Methods of Segregation Analysis.” In Modern Statistical Methods in Chronic Disease Epidemiology, eds. S. H. Moolgavkar & R. L. Prentice. New York: Wiley, pp. 213–224.
Falconer, D. S. (1989). Introduction to Quantitative Genetics (3rd ed.). London: Longman.
Hartl, D. L., & Clark, A. G. (1989). Principles of Population Genetics (2nd ed.). Sunderland, MA: Sinauer.
Hedrick, P. W. (1985). Genetics of Populations. Boston, MA: Jones and Bartlett.
Kahn, P., & Graf, T. (Eds.). (1986). Oncogenes and Growth Control. New York: Springer-Verlag.
Levitan, M. (1988). Textbook of Human Genetics. New York: Oxford University Press.
Lubin, J., & Bale, S. (1987). “Detection of Excess Risk in Family Data” (letter with reply). Genetic Epidemiology, 4, 451–456.
Lynch, H. T., Kimberling, W. J., Biscone, K. A., Lynch, J. F., Wagner, C. A., Brennan, K., Mailliard, J. A., Johnson, P. S., Soori, J. S., & McKenna, P. J. (1986). “Familial Heterogeneity of Colon Cancer Risk.” Cancer, 57, 2089–2096.
Manton, K. G., Malker, H., & Malker, B. (1986). “A Comparison of Temporal Change in U.S. and Swedish Lung Cancer 1950–51 to 1981–82.” Journal of the National Cancer Institute, 77, 665–675.
Manton, K. G., & Soldo, B. J. (1985). “Dynamics of Health Changes in the Oldest Old: New Perspectives and Evidence.” Milbank Memorial Fund Quarterly I Health and Society, 63, 206–285.
Manton, K. G., & Stallard, E. (1984). Recent Advances in Mortality Analysis. New York: Academic Press.
— (1988). Chronic Disease Modelling. Oxford, UK: Charles Griffin.
Marx, J. (1990). “Many Gene Changes Found in Cancer.” Science, 246, 1386–1388.
McKay, F. W, Hanson, M. R., & Miller, R. W. (1982). Cancer Mortality in the United States, 1950–1977, National Cancer Institute Monographs, No. 59. Washington, DC: U.S. Government Printing Office.
Moolgavkar, S. H. (1986). “Hormones and Multistage Carcinogenesis.” Cancer Surveys, 5, 635–648.
Moolgavkar, S. H. (In press). “Stochastic Models of Carcinogenesis. In Handt ok of Statistics (Vol. 8), eds. C. R. Rao & R. Chakraborty. New York: Elsevier.
Morton, N. E. (1982). Outline of Genetic Epidemiology. Basel, Switzerland: Karger.
Morton, N. E., and Maclean, C. J. (1974). “Analysis of Family Resemblance. Ill: Complex Segregation of Quantitative Traits.” American Journal of Human Genetics, 26, 489–503.
Motulsky, A. G., Burke, W., Billings, P. R., & Ward, R. H. (1987). “Hypertension and the Genetics of Red Cell Membrane Abnormalities.” In Molecular Approaches to Human Potygenic Disease, CIBA Foundation Symposium, No. 130, eds. G. Bock & G. M. Collins. Chichester, UK: Wiley, pp. 150–160.
Nei, M. (1987). Molecular Evolutionary Genetics. New York: Columbia University Press.
Nei, M., Fuerst, P. A., & Chakraborty, R. (1976). “Testing the Neutral Mutation Hypothesis by Distribution of Single Locus Heterozygosity.” Nature, 262, 491–493.
Ott, J. (1985). Analysis of Human Genetic Linkage. Baltimore, MD: Johns Hopkins University Press.
Robertson, A. (1967). “The Nature of Quantitative Genetic Variation.” In Heritage From Mendel, ed. R. A. Brink. Madison: University of Wisconsin Press, pp. 265–280.
Schottenfeld, D., & Fraumeni, J. F (1981). Cancer Epidemiology and Prevention. Philadelphia, PA: Saunders.
Schwartz, A. G., Boehnke, M., & Moll, P. P. (1988). “Family Risk Index as a Measure of Familial Heterogeneity of Cancer Risk: A Population-Based Study in Metropolitan Detroit.” American Journal of Epidemiology, 128, 524–535.
Sing, C. F., & Boerwinkle, E. (1987). “Genetic Architecture of Inter-individual Variability in Apolipoprotein, Lipoprotein and Lipid Phenotypes.” In Molecular Approaches to Human Polygenic Disease, CIBA Foundation Symposium, No. 130, eds. G. Bock & G. M. Collins. Chichester, UK: Wiley, pp. 99–121.
Sing, C. F., Boerwinkle, E., Moll, R P., & Templeton, A. R. (1988). “Characterization of Genes Affecting Quantitative Traits in Humans.“ In Proceedings of the 2nd International Conference on Quantitative Genetics, eds. B. S. Weir, E. J. Eisen, M. M. Goodman, & G. Namkoong. Sunderland. MA: Sinauer, pp. 250–269.
Teich, N. M. (1986). “Oncogenes and Cancer.” In Introduction to the Cellular and Molecular Biology of Cancer, eds. L. M. Franks & N. M. Teich, Oxford. UK: Oxford University Press, pp. 200–228.
Thompson, J. S., & Thompson, M. W. (1986). Genetics in Medicine (4th ed.). Philadelphia, PA: Saunders.
Trussell, J., & Rodriguez, G. (In press). “Heterogeneity in Demographic Research.” In Convergent Questions in Genetics and Demography, eds. J. Adams, A. Hermalin, D. Lam, & P. E. Smouse. New York: Oxford University Press. UNSCEAR (United Nations Scientific Committee on the
Effects of Atomic Radiation. (1988). “Radiation Carcinogenesis in Man.” In Sources, Effects, and Risks of Ionizing Radiation. New York: United Nations, pp. 405–543.
Vaupel, J. W. (1988). “Inherited Frailty and Longevity.” Demography, 25, 227–287.
Vaupel, J. W. (In press-a). “Kindred Lifetimes: Frailty Models in Population Genetics.” In Convergent Questions in Genetics and Demography, eds. J. Adams, A. Hermalin, D. Lam, & P. E. Smouse. New York: Oxford University Press.
Vaupel, J. W. (In press-b). “Relatives' Risks: Frailty Models of Life History Data.” Theoretical Population Biology.
Vaupel, J. W., Manton, K. G., & Stallard, E. (1979). “The Impact of Heterogeneity on Individual Frailty on the Dynamics of Mortality.” Demography, 16, 439–454.
Vaupel, J. W, & Yashin, A. I. (1985). “Heterogeneity's Ruses: Some Surprising Effects of Selection on Population Dynamics.” The American Statistician, 39, 176–185.
Vogel, F., & Motulsky, A. G. (1986). Human Genetics (2nd ed.). New York: Springer-Verlag.
Weiss, K. M. (1985). “Phenotype Amplification' as Illustrated by Cancer of the Gallbladder in New World Peoples.” In Etiology of Complex Diseases in Small Populations: Ethnic Differences and Research Approaches, eds. R. Chakraborty & E. J. E. Szathmary. New York: Liss, pp. 179–198.
— (1989). “Are the Known Causes of Death Related to the Human Life Span and Its Determination?” American Journal of Human Biology, 1, 307–320.
Weiss, K. M. (In press-a). “Biology, Homology, and Epidemiology.” In Convergent Issues in Genetics and Demography, eds. A. Hermalin, J. Adams, D. Lam, & P. E. Smouse. New York: Oxford University Press.
Weiss, K. M. (In press-b). “Medieval Mappaemundi and the Conceptual Map of Genetics.” In Papers in Honor of William J. Schull (as yet untitled festschrift volume), eds. C. F. Sing & C. L. Hanis. Oxford, UK: Oxford University Press.
Weiss, K. M., & Chakraborty, R. (1984). “Multistage Models and the Age Pattern of Familial Polyposis Coli.” Cancer Investigation, 2, 443–448.
— (1990). “Multistage Models and the Age-Patterns of Cancer: Does the Statistical Analogy Imply Genetic Homology?” In Familial Adenomatous Polyposis, ed. L. Herera. New York: Liss, pp. 79–91.
Weiss, K. M., Chakraborty, R., Majumder, P. P., & Smouse, P. E. (1982). “Problems in the Assessment of Relative Risk of Chronic Disease Among Biological Relatives of Affected Individuals.” Journal of Chronic Diseases (now Journal of Clinical Epidemiology), 35, 539–551.
Weiss, K. M., Chakraborty, R., Smouse, P. E., Buchanan, A. V., & Strong, L. C. (1986). “Familial Aggregation of Cancer in Laredo, Texas: A Generally Low-Risk Mexican-American Population.” Genetic Epidemiology, 3, 121–143.
Weiss, K. M., Ferrell, R. E., & Hanis, C. L. (1984). “A New World Syndrome of Metabolic Diseases With a Genetic and Evolutionary Basis.” Yearbook of Physical Anthropology, 27, 153–178.
White, R., & Lalouel, J.-M. (1987). “Investigation of Genetic Linkage in Human Families.” Advances in Human Genetics, 16, 121–228.
Whittemore, A., & Keller, J. B. (1978). “Quantitative Theories of Carcinogenesis.” SIAM Review, 20, 1–30.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Weiss, K.M. The Biodemography of Variation in Human Frailty. Demography 27, 185–206 (1990). https://doi.org/10.2307/2061448
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.2307/2061448