摘要:

AbstractDiastolic blood pressure readings taken in 1983–1984 on 1,474 Greek individuals (628 living on the island of Levkada, 846 relatives having migrated to Melbourne, Australia) from 204 two generational pedigrees were analysed. Blood pressure was regressed as a quadratic in age by sex and migrant status, and on temperature. Variance increased with age and was greater in migrant males. The covariance between relatives in different countries was significant. Variation was modeled by a multivariate normal model for pedigree analysis in terms of genetic effects, a common environment effect, and effects particular to an individual. The genetic component was 25.9 mm Hg2, independent of sex and migrant status. Importantly, the common environment component was not significant. The third component was greatest in migrant males. Spouse correlation was −0.09 (SE = 0.03). Exclusion of 86 individuals who reported currently receiving medication for elevated blood pressure stabilised the variance and decreased the genetic component. The data suggest that familial aggregation of diasatolic blood pressure is due to genetic factors which produce the same variation in males and females, living on Levkada or in Melbourne. Nongenetic factors explain the greater variation in blood pressure of migrant males living in Melbourne. © 1992 Wiley‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370090402

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

年代:1992

数据来源: WILEY

摘要:

AbstractEstimates of the impact of apolipoprotein E (apo E) alleles coding for the three common isoforms on plasma lipid levels assume genetic homogeneity among the genotype classes. To test this assumption, we have determined the apo E genotype at the two common polymorphic sites (amino acids 112 and 158) by DNA amplification and hybridisation with allele‐specific oligoprobes, in 195 unrelated Caucasian participants of the Rochester Family Heart Study previously classified as heterozygotes by isoelectric focusing (IEF). Fourteen discordant samples were initially detected. Repeat typing of these samples by both methods resolved nine discrepancies and analysis of additional blood samples from the remaining five individuals eliminated a further four discrepancies. The only truly discordant allele was found in a female subject who had an E3 isoform with the common E2 (Cys112, Cys158) genotype. Transmission of this allele from the mother was demonstrated. From these results, we estimate the frequency of discrepancies between isoforms and common genotypes to be 0.25% in this population. Allele misclassification was caused by poor amplification of the DNA in six samples and superimposition of glycosylated and nonglycosylated apo E isoforms on isoelectric focusing gels in five samples. We conclude that the assumption of genetic homogeneity among genotype classes is valid and that misclassification due to technical difficulties is more frequent than true discordancies. © 1992 Wiley‐Liss,

ISSN:0741-0395    

DOI:10.1002/gepi.1370090403

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

年代:1992

数据来源: WILEY

摘要:

AbstractWe have examined whether variation at the apolipoprotein (apo) B, apo E, apo AII, and apo AI‐CIII‐AIV genes affected the relationship between dietary intake and serum lipid traits in individuals who had participated in dietary intervention from a basal high fat diet to a low fat diet followed by a return to their natural diet, the switchback. On both the basal and switchback diets where the variance of dietary intake was great, there was a significant correlation between P/S ratio and serum total, low‐density lipoprotein (LDL) cholesterol, and apo A1 levels. In addition dietary cholesterol (dchol) levels correlated significantly with serum apo A1 levels on the basal diet. Comparing the difference between basal and intervention (Δ1) and between switchback and intervention diets (Δ2), changes in dchol and P/S ratio correlated significantly with changes in serum total, high‐density lipo‐protein (HDL) and LDL cholesterol, and apo B levels. There was a significant correlation between monounsaturated fatty acid (MUFA) and apo A1 levels during both changes. Furthermore we have examined whether the relationship between variables was homogeneous among genotypes of candidate gene polymorphisms. A heterogeneous effect (P<0.01) was seen among genotypes of thePvuII‐AIV restriction fragment length polymorphism (RFLP) on the correlation of serum LDL cholesterol levels and dietary MUFA during both dietary changes (Δ1 and Δ2). A heterogeneous effect among genotypes of the apo BXbaI RFLP on the correlation between dchol versus total and LDL cholesterol during the change Δ1, but not Δ2, was observed. Thus our results show that both dietary components and genetic variation affect the response of serum lipid, lipoprotein, and apolipoprotein levels to dietary change. © 19

ISSN:0741-0395    

DOI:10.1002/gepi.1370090404

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

年代:1992

数据来源: WILEY

摘要:

AbstractData on 337 lung cancer families were analyzed to determine if known cohort differences in parental cigarette consumption influence parameters from a segregation analysis. Previous results suggested that, after allowing for an individual's pack‐years of tobacco exposure, Mendelian codominant inheritance of an allele that produced an earlier age of onset provided a good fit to the data. In the present study, the data were split into two groups of families: probands age 60 and over (born before WWI) and probands younger than age 60. This partition of the data by age of the proband was done to separate families in which there were parents who were less likely to smoke from those with parents more likely to smoke—predicated on the known increase of smoking prevalence after World War I. For the younger proband families (those with parents more likely to smoke), only Mendelian codominant inheritance adequately fit the data. The hypotheses of no major type, environmental transmission, and Mendelian dominant or recessive inheritance were rejected. In contrast to our earlier findings, the estimate of population susceptibility increased from 28% in the total data to 60% in this subset. In the older proband families (those with parents less likely to smoke), the no major type and environmental hypotheses were rejected; further, none of the Mendelian models could be distinguished. Our results demonstrate that cohort differences, probably in exposure to tobacco, can confound parameters of a segregation analysis, and suggest that the genetic component of lung cancer may be greater than previously estimated. It further suggests that susceptibility to lung cancer occurs as a function of susceptibility to the effects of tobacco smoking. © 1992 Wiley‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370090405

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

年代:1992

数据来源: WILEY

摘要:

AbstractThis paper presents an elementary statistical method for analyzing dichotomous outcomes in unselected samples of twin pairs using stratified estimators of the odds ratio. The methodology begins by first randomly designating one member of each twin pair as an ‘index’ twin and the other member as the ‘co‐twin.’ Stratifying on zygosity, odds ratios are used to measure the association between disease in the index twin and disease in the co‐twin. From these zygosity‐specific tables we cal‐culate the Woolf‐Haldane estimator of the common odds ratio (ψF, the weighted average of the zygosity‐specific odds ratios), the Mantel‐Haenszel test statistic (χ M‐H2) for the common odds ratio, and a test (χ G2) for the difference in the zy‐gosity‐specific odds ratios. In this application, ψFprovides an estimate of the familial association for disease and the accompanying χ M‐h2provides a test of the null hypothesis, ψF= 1 (i.e., there is no evidence for a familial influence on disease). The χ G2is a test of the null hypothesis that ψMZ= ψDZ; a significant value for χ G2suggests a genetic influence on disease (assuming that the observed odds ratios follow a pattern where ψMZ>ψDZ). A new test statistic (χ c2) is proposed that incor‐porates the expectation that ψMZ= ψ DZ2under a purely additive genetic model with no common environmental effects. A significant value of χ c2indicates that the different odds ratios across zygosity are partly due to common environmental influences. Conversely, a nonsignificant value of χ Gcis an indication that the zygosity‐specific odds ratios are due solely to additive genetic effects and not to common environment. This basic approach is extended to examine the effects of measured indicators of the specific environment and the assessment of certain forms of gene by environment interaction. All of the methods are easily understood, highly flexible, readily computed using a hand calculator, and incorporate the inherent genet

ISSN:0741-0395    

DOI:10.1002/gepi.1370090406

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

年代:1992

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370090407

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

年代:1992

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370090408

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

年代:1992

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370090401

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

年代:1992

数据来源: WILEY