The purpose of this commentary is to provide a framework for using the well-known sib-pair methodology in the context of epidemiologic study designs. Using examples from the Pittsburgh family studies of insulin-dependent diabetes mellitus, we illustrate that the sib-pair method can be used in family-based epidemiologic studies. In a cohort study, unaffected relatives of probands ascertained from well-defined populations are followed for disease development. Disease risks are then stratified according to the number of alleles at one or more loci (0, 1, 2) that are identical by descent (ibd) with the proband. In the absence of linkage between the marker locus and the disease locus, disease risks are expected to be identical in the three groups. Measures of relative risk can be computed (with share-0 as baseline group). In a case-control study, relatives of probands that become affected (cases) are compared to a sample of relatives of probands that stay unaffected (controls) with respect to the number of alleles ibd with the proband. Measures of odds ratio can be computed (with share-0 as baseline group). In both cohort and case-control approaches, covariates including other genetic markers and environmental exposures can be evaluated in relation to disease risk and also for evidence of interaction with the specific marker of interest using stratified and multivariate analyses. Family-based epidemiologic studies allow investigators to study, in a single design, the role of environmental factors and specific gene loci in the etiology of diseases.
Epidemiological techniques have been utilized to accumulate new knowledge about insulin-dependent diabetes mellitus (IDDM), leading to important insights into the disease process and the alteration of these mechanisms when viewed from a geographic or population base. More recently, highly powerful and sophisticated techniques of molecular biology have been added to the research arsenal, extending the knowledge on the genetic basis for IDDM and the probable environmental factors involved. The development and growth of the new discipline of epidemiological genetics promises exciting new developments for the future of our field as well as that of other major medical problems having a genetic base, but significantly influenced by environmental factors. This review stresses the importance of carefully validated diabetes registries in the study of the epidemiology of IDDM. The Children's Hospital of Pittsburgh and the University of Pittsburgh Medical Center have spear-headed the development of such registries, worldwide. The first international meeting on IDDM epidemiology in 1983 gave as a result, i.e., the finding that there were truly remarkable differences in the risk of developing IDDM depending upon the geographic location of the individual. Later collaborative work via the Diabetes Epidemiology Research International (DERI) group has confirmed the previous finding and added the description of secular trends and epidemics of IDDM. It is remarkable that the incidence rate of IDDM in children below 15 years vary from 1/100,000/yr in the Orient to 35/100,000/yr in Finland. The epidemiological approach in the study of IDDM has also stimulated research into the various facets of the etiology of the disease, genetic factors, autoimmune mechanisms and environmental factors.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence rate in Barbados falls near the lower limits of rates reported for Caribbean populations. There was a marked seasonal effect among males, even though the climate varies little throughout the year. This observation, and the incidence peak during 1984-1985, provide support for the role of environmental factors in the etiology of IDDM.
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