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The Value of Sibling and Other 'Relational' Data for Biodemography and Genetic Epidemiology
Pages 110-132

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From page 110...
... This is true for qualitative traits such as presence or absence of disease as well as for quantitative traits that are characterized by a continuous range of variability in the population. From the perspective of evolutionary theory, it is desirable to maintain the broadest range of opportunities to respond to varying environmental circumstances in order to optimize the likelihood of survival in the face of potentially rapid fluctuations in environmental circumstances.
From page 111...
... Genetic epidemiology incorporates the perspective of several different disciplines. However, much research that is considered to be genetic epidemiology is geared towards characterizing genetic effects in the context of a complex system rather than fully integrating information about the effects of both genetic and environmental influences on health-related outcomes.
From page 112...
... The informativeness of sibling data in addressing issues of variability in this context is explored. SOURCES OF VARIABILITY FOR QUANTITATIVE TRAITS The theoretical basis of genetic and environmental influences on a trait was developed from a number of perspectives, with Fisher (1918)
From page 113...
... In general, traits that are relevant for aging-related research are likely to exhibit genetic influences that are more complex than single major genes or are likely to occur at too rare a frequency to be a major focus of population-based survey research. Polygenic Variance Extensive theoretical development has occurred in quantitative genetics over nearly a century.
From page 114...
... These efforts are designed to permit detection of loci of relatively small individual impact on complex traits, especially chronic disease traits. Latent Effects Variance decomposition models conceptualize genetic effects as latent, unobservable factors that are assessed as components of variation within a population.
From page 115...
... Major Effects Major environmental influences can be characterized as qualitative variables such as exposure or nonexposure to an environmental risk factor. This kind of major environmental factor can be readily incorporated into quantitative genetic models either as a covariate or as a variable that distinguishes among multiple subgroups that can be compared for differences in covariance structure (e.g., Sorbom, 1974~.
From page 116...
... While any general model needs to include random variability in a measurement model, true environmental effects could consist of any combination of random effects, nonrandom quantitative effects, and/or major effects. Latent Effects As with genetic effects, the quantitative genetic model incorporates environmental influences as latent effects that can be either unique to the individual or shared by family members.
From page 117...
... Some study designs are more effective in distinguishing shared genetic effects from shared environmental effects. All study designs rely on a fairly strong set of assumptions regarding environmental influences.
From page 118...
... . It is not possible to distinguish between shared genetic influences and shared family environmental influences in nuclear families without measuring at least one of these influences.
From page 119...
... The key advantage of adoption studies is that they provide a direct and powerful test of the distinction between genetic influences and shared environmental influences. Potentially powerful information about prenatal effects can also be obtained from the full adoption design.
From page 120...
... Since there is only a single meiosis between one generation and the next, linkage disequilibrium is expected within families for a linked marker and trait locus even if the population is in equilibrium. Linkage Analysis of Pedigree Data Classical LOD score linkage analysis of pedigree data (Ott, 1991)
From page 121...
... The advantage of using sib-pair analysis from a genetic perspective is that it moves analysis one step closer to localization of specific genes that influence complex quantitative traits. For such traits, there are likely to be multiple genetic effects explaining modest proportions of the total phenotypic variance.
From page 122...
... Each of these approaches can be readily implemented into a general model for the analysis of multiple phenotypes in an arbitrary sibship structure (Vogler et al., 1997~. Sib extensions of large-scale survey research projects can be highly effective for gene mapping studies of complex traits.
From page 123...
... Recent admixture of two populations that differ in marker allele frequencies and trait locus allele frequencies will also exhibit spurious associations (Ewens and Spielman, 1995) until a sufficient number of generations of random mating and recombination move the population to a new equilibrium.
From page 124...
... While the TDT tests were originally developed and extended for application to qualitative disease traits, recent extensions have been made to accommodate continuously distributed quantitative traits (Allison, 1997; Rabinowitz, 1997~. George et al.
From page 125...
... One of the great potential uses of these models is in incorporating environmental assessment into the models in a manner similar to how genetic marker information has been incorporated into the genetic aspects of the models. ENVIRONMENT "MAPPING" The analogy between mapping specific genetic effects and specific environmental effects is not perfect; we do not have an environmental analogy of the genetic map with markers pointing to positions of tightly linked factors for environmental influences, but we can specify candidate environmental agents analogous to specifying candidate genes.
From page 126...
... A systematic effort to enhance the environmental side using large-sample population-based sibling data would be valuable for enhancing the ability to understand the total constellation of multiple genetic and environmental influences on complex traits. OPPORTUNITIES FOR INTEGRATED MODELS Taking advantage of advances in molecular genetics, powerful methods have been developed recently to detect individual loci that contribute a relatively modest amount to the total phenotypic variance based on sibling TDT approaches.
From page 127...
... Cookson 2000 A general test of association for quantitative traits in nuclear families. American Journal of Human Genetics 66:279-292.
From page 128...
... American Journal of Human Genetics 31:176-198. 1979b Multifactorial inheritance with cultural transmission and assortative mating.
From page 129...
... Rao 1996 Combining extremely concordant sibpairs with extremely discordant sibpairs provides a cost effective way to linkage analysis of quantitative trait loci. Genetic Epidemiology 13:513-533.
From page 130...
... Botstein 1989 Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121:185-199.
From page 131...
... Rosenberg 1999 Use of unlinked genetic markers to detect population stratification in association studies. American Journal of Human Genetics 65:220-228.
From page 132...
... Tarantino, and J.R. Fernandez 1997 A multivariate model for the analysis of sibship covariance using marker information and multiple quantitative traits.


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