ISSN:0741-0395    

DOI:10.1002/gepi.1370010402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractIn most genetic studies in humans the variability in a quantitative trait is adjusted for variability in concomitants (age, sex, etc) using a single regression equation prior to analyses of pedigree data. To illustrate an alternative approach, a single locus genetic model was tested. This model incorporates genotypic effects on the level of the trait, the variability in the trait, and the relationship between a concomitant and the trait. In this study, the model was applied to measures of age and low‐density lipoprotein (LDL) cholesterol in a large kindred with familial hypercholesterolemia. The application of this model to 322 individuals in four generations provided evidence that genotypic variation at a single locus influences LDL levels early in life, the rate of increase of LDL with age and the phenotypic variance. A model with genotype‐dependent slope and variance fit the data signifcantly better than a model with slope and variance independent of genotype. The inclusion of age‐specific genotypic differences contributed to identification of high‐risk individuals, to statistical support for a major locus, and to evidence for genetic determination of the tracking of LDL levels. Models that incorporate genotype‐specific concomitant effects have the potential to represent more realiscally the relationship between genotypic variability and quantitative phenotypic variation than models that assume that these effects do

ISSN:0741-0395    

DOI:10.1002/gepi.1370010403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractPopulation‐based data on 1,842 subjects from six semitraditional Pacific communities, collected in the years 1978–1983, have been compared in order to examine the hypotheses that differences in the distribution of plasma glucose concentration between populations are to some extent genetically determined, and that non‐Austronesian (NAN) Melanesians are relatively resistant to glucose intolerance. Semitraditional communities were chosen for study so that the comparison would be minimally confounded by either known or as yet undetermined environmental factors associated with nontraditional living, the effects of which may vary between populations. The samples were also selected so as to provide a gradient of proportional NAN and AN admixture. They were drawn from the following regions: the highlands of Papua New Guinea, New Caledonia, Fiji, the Wallis Islands, Western Samoa, and Kiribati (formerly the Gilbert Islands). The Papua New Guinea highlanders, of entirely NAN ancestry, were regarded as the baseline population.A gradient of increasing mean 2‐hr plasma glucose concentration was observed across the six populations and differences persisted between populations, after controlling for age and obesity. Variations in diet, physical activity, and degree of sociocultural modernization were not considered a sufficient or consistent explanation of these findings and they therefore lend tentative support to the hypothesis of a genetic component to variability in glucose tolerance.The relationship between population estimates of glucose tolerance and estimates of the genetic distance from the baseline NAN Melanesian sample was examined. With the notable exception of Fiji, there was evidence of a linear correlation between the two par

ISSN:0741-0395    

DOI:10.1002/gepi.1370010404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractWithin a family, associations between a disease and a marker locus are often inferred when affected offspring share marker alleles more often than is expected by chance. Generally, this is due to nonrandom parental transmission of marker alleles and specifically could be due to linkage, epistatic gene action, or segregation distortion at the marker locus. In this paper, we discuss the statistical properties of a general test of nonrandom segregation of a marker gene. The exact probability distribution of the test under the null hypothesis of random segregation is derived, as is the distribution under the alternative hypothesis of genetic linkage. We compute the mean and variance of these distributions as a means of judging the adequacy of random segregation to explain disease‐marker data but also provide a method for computing the exact significance value under the null hypothesis. These methods have been utilized for studying HLA segregation in families with tuberculoid leprosy. On the assumption that this type of leprosy is autosomal recessive, we find evidence that a gene controlling susceptibility to infection by Mycobacterium leprae resides on human chromosome 6, approximately 13 map units away from the HLA locus in male

ISSN:0741-0395    

DOI:10.1002/gepi.1370010405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractOur specific aim in this study was to investigate commingling and family resemblance for fasting blood glucose in 160 randomly selected white families from the Princeton School District Lipid Research Clinics Family Study. Adjustment of fasting blood glucose for the influence of age, sex, and the use of oral contraceptives and construction of indices were performed simultaneously using multiple regression methods. Path analysis was carried out, constructing an environmental index based on special diet usage, hematocrit, and obesity, which was also adjusted for the influences of age and sex. Commingling analysis and segregation analysis using the mixed model were also performed. Nearly 16% of the variance of fasting blood glucose was accounted for by age and sex. Obesity itself, which constituted the index, explained an additional 4% of the variance of fasting blood glucose. Significant genetic heritability for fasting blood glucose was documented by both path analysis and segregation analysis. In aggregate, we conclude that though there was a major familial vector accounting for within‐family aggregation of blood glucose, it was probably generated by a multifactorial component as compared to a major locus. Under the most parsimonious model, path analysis estimated the genetic and cultural heritabilities as h2= .39 ± .08 and c2= .06 ± .03., respectiv

ISSN:0741-0395    

DOI:10.1002/gepi.1370010406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractThe problem discussed is that of interpreting LOD scores when multiple markers are tested for linkage with a particular disease locus. Provided the tests are based on independent segregations, both the maximum and the average LOD can be translated into a score that would have the same significance level were it the result of a single test.

ISSN:0741-0395    

DOI:10.1002/gepi.1370010407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractWe present evidence of a pedigree in which a major gene for breast cancer‐susceptibility appears to segregate in a dominant fashion. Linkage analysis suggests that the breast cancer‐susceptibility locus in this family may be linked to theABOlocus, which is located on band q34 of chromosome 9. At an early stage in the analysis, a LOD score of 3.0 for zero recombination was obtained for linkage betweenABOand the susceptibility locus, but a single recombinant reduced the LOD score to 1.72 at a recombination fraction of 0.06. A final observation of a nonrecombinant brings the LOD score for this pedigree to 1.99 at\documentclass{article}\pagestyle{empty}\begin{document}$\documentclass{article}\pagestyle{empty}\begin{document}$ \widehat{\rm{\theta }} $\end{document}$\end{document}= 0.05. We attempt to put these results in perspective by discussing the sensitivity of the LOD score to the next observation. Examples of the volatility of LOD scores are given. These simple calculations show that tight linkage represents the worst case for the interpretation of a LOD score of 3.0. Finally, we discuss the linkage between the breast cancer‐susceptibility locus and theABOblood group and approaches to confirming or denying this r

ISSN:0741-0395    

DOI:10.1002/gepi.1370010408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractWe studied 52 families having more than one member affected with insulin‐dependent diabetes mellitus (IDDM) for linkage of an IDDM‐susceptibility locus to the immunoglobulin lociKMandGM. Linkage was analyzed by the LOD score method using single‐locus recessive and dominant models of IDDM inheritance, with penetrances of the disease‐susceptible genotypes being dependent on age and reaching a maximum of 20% by age 40. We found no evidence for linkage of IDDM toKMorGM. Close linkage (recombination fraction<5%) was rejected forKMunder the recessive model and forGMunder both models. These results suggest either that there are no IDDM‐susceptibility loci closely linked toKMorGMor that use of a single‐locus model of IDDM (which ignores the effects of the susceptibility locus in theHLAregion) is inadequate for thei

ISSN:0741-0395    

DOI:10.1002/gepi.1370010409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractWe have been investigating cancer patterns in the Hutterites, a religious isolate residing on communal farms [Martin et al, 1980a,b,c]. Advantages of this population include extensive and accurate genealogies, essentially complete case ascertainment, and relatively uniform environmental background with regard to geographic location, lifestyle, and diet. However, application of the common epidemiological approach to familial risk assessment based on incidence in relatives of index cases [Haenszel, 1959]posed difficulties because all cases are probands. We also planned to employ matching to control for important confounders and thus had to deal with the problems of the matching of cases and controls as well as the existence of complex inbreeding [Hauck and Martin, 1982]. Our basic approach was to compare coefficients of kinship (Fm, a measure of coancestry) of cases with each other to coefficients between cases and matched controls drawn from the same population. We have developed a paired t‐type statistic to assess the significance of observed differences.We present, as examples, application of our methods to the analysis of Hutterite data on neurofibromatosis, known to be inherited in autosomal dominant fashion, and on cancer. Neurofibromatosis showed significant familial aggregation, as expected. Breast, colon‐rectal, and stomach cancer did not. We then show how to evaluate power and to determine appropriate sample sizes for detecting specified increases in kins

ISSN:0741-0395    

DOI:10.1002/gepi.1370010410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370010401

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY