摘要:

AbstractDetection of familial aggregation of a disease is important for studying possible genetic and environmental factors contributing to disease etiology. Accurate quantification of familial aggregation can provide guidance for subsequent, more sophisticated genetic studies. This article presents a statistical model and method for detecting both inter‐ and intra‐class aggregation of a binary trait with family data. The method used here is based on the logistic regression model which incorporates effects of individual covariates while measuring familial aggregation of risk as the odds ratios among classes of relatives. An estimation equation approach is presented where the joint distribution of binary traits among family members need not be fully specified. Data from a genetic epidemiologic study on liver cancer in Shanghai are analyzed for illustration, and reveal strong aggregation of risk even after adjusting for covariates. Effects of non‐random sampling and ascertainment bias are also disc

ISSN:0741-0395    

DOI:10.1002/gepi.1370080602

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

年代:1991

数据来源: WILEY

摘要:

AbstractIn the National Heart, Lung, and Blood Institute Twin Study, body mass index (BMI) was studied at military induction and at three subsequent examinations spanning five decades in a cohort of white, male World War II veterans. At military induction (1940s) and again at the first clinical examination of this study (1969–1973), there was close agreement of three commonly used estimates of heritability (range 0.72 to 0.80), and no evidence of a difference in total variance of BMI between the zygosities. However, at the last two examinations (1980s), the total variance in dizygotic (DZ) twins was significantly greater than that of monozygotic (MZ) twins (P<0.01) and these same heritability estimates varied widely. The among‐pair estimate of heritability fell to unrealistic negative values, the within‐pair estimate rose to values of 1.0 or greater, and the intraclass correlation coefficient estimate was slightly lower than in the entire cohort at baseline. The cause of the unequal zygosity total variance appears to have been nonparticipation at later examinations of MZ twins with extreme values of BMI, with no evidence of a similar selection process influencing DZ twins. This selection process biased the three estimates of heritability, making it difficult to determine which estimate is the most appropriate. Despite these biases, it remains clear that genetic factors contribute substantially to BMI in this popul

ISSN:0741-0395    

DOI:10.1002/gepi.1370080603

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

年代:1991

数据来源: WILEY

摘要:

AbstractA variability gene model [Magnus et al.,Clin Genet19:67–70, 1981] hypothesizes that environmental influences on the expression of additive genes for a quantitative trait such as cholesterol are under the control of alleles at a separate nonadditive locus. They suggest identifying such genes using an analysis of variance to compare absolute intrapair monozygotic twin trait differences between the genotypes of the postulated variability locus. However, quantitative traits such as cholesterol often have skewed distributions with a long right tail; what are the effects of such nonnormality on the procedure suggested by Magnus et al. [1981]? We show that their method is a special case of the Levene tests, robust tests for variability differences. We introduce a statistical model representing sources of variability in twin pair differences and demonstrate with simulation studies that although the Levene tests have robust Type I error, power is enhanced when nonnormal data are transformed before analysis, and the apparent presence and degree of variability differences are dependent on the scale of analysis. These findings indicate the importance of appropriate transformation of the trait before analysis. Analysis of a well‐characterized twin data set illustrates these conclusi

ISSN:0741-0395    

DOI:10.1002/gepi.1370080604

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe have investigated the effect of apolipoprotein (apo) E polymorphism on serum lipid, lipoprotein, and apolipoprotein levels in a sample of 195 children, aged 8–11 years, from Sezze, Central Italy. The relative frequencies of e2, e3, and e4 alleles were 0.062, 0.867, and 0.072, respectively. Variation at the apo E gene locus explained 5.1% of the sample variance in serum total cholesterol levels, 7.6% in low‐density lipoprotein (LDL) cholesterol levels, 7.3% in apo B levels, and 14.1% in high‐density lipoprotein‐apo E (HDL‐E) levels. The effect of the e2 allele was to lower levels of total cholesterol, LDL‐cholesterol, and apo B and to raise levels of HDL‐E, while the effect of the e4 allele was the opposite. Variation at the apo E gene locus was not associated with differences in serum triglyceride, HDL‐cholesterol, or apo AI levels. The effects of common apo E polymorphisms and genetic variation associated with thePvuII RFLP of the apo B gene on serum apo B levels were additive, explaining 11.3% of the phenotypic variance in this sample. When the effect of apo E polymorphism on serum lipid traits was estimated in boys and girls separately, variation at the apo E gene locus explained 10.4, 13.3, 13.3, and 13.5% of the phenotypic variance in serum total cholesterol, LDL‐cholesterol, apo B, and HDL‐E levels, respectively, in boys, while in girls only the effect on HDL‐E levels (19.3%) reached statistical significance. This study has demonstrated that genetic variations at the apo E locus contribute to the determination of serum lipid, lipoprotein, and apolipoprotein levels in youths and that the effect

ISSN:0741-0395    

DOI:10.1002/gepi.1370080605

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

年代:1991

数据来源: WILEY

摘要:

AbstractSib‐pair methods provide simple, robust, easily implemented ways to screen for linkage between a marker locus and a suspected disease susceptibility locus. The basic analysis reflects the idea that, in the presence of linkage, siblings who share more alleles at the marker locus should also tend to be concordant for disease. Available sib‐pair methods do not lead directly to estimates of risk associated with nongenetic factors, may not account for a variable age‐at‐onset, or may require that the age‐at‐onset distribution be known. In this paper, we propose a method for sib‐pair linkage analyses that allows for a variable age‐at‐onset using a logistic model, easily allows modelling of nongenetic factors, reflects the correlation of sibs within a sibship, and allows for nonzero risk in those without the susceptibility genotype. Based on a limited number of simulations, the method has as good or better power than another recently described method that also allows for a vari

ISSN:0741-0395    

DOI:10.1002/gepi.1370080606

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

年代:1991

数据来源: WILEY

摘要:

AbstractSystemic lupus erythematosus (SLE) is a complex disease which is partly determined by genetic factors which influence susceptibility to the disease phenotype. In this association study we try to define the high risk haplotypes which are responsible for this disease, together with other environmental factors. In many other association studies a set of SLE patients is compared to a set of controls. The basic assumption about the underlying population is that the disease and control sample should originate from the same genetic population, which is not always completely satisfied in many studies. Therefore, we analyse our family data by applying the Haplotype Frequency Difference (HFD) Method, which constructs its internal control group from those haplotypes not transmitted to the affected individual. Results partially conform with other studies, showing that the haplotypes B8 DR3 as well as B7 DR2 have a high positive association with SLE. When the DR locus was analyzed alone, we found besides the alleles DR2 and DR3 a negative association for DR1, DR5, and DR6.

ISSN:0741-0395    

DOI:10.1002/gepi.1370080607

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

年代:1991

数据来源: WILEY

摘要:

AbstractHereditary hematologic disorders (HHD) have been reported in excess among infants and families of infants with congenital cardiovascular malformations (CCM) compared with controls, suggesting possible common pathogenetic mechanisms. It is plausible that hemodynamic changes during pregnancy associated with HHD could affect cardiac morphogenesis. To investigate whether offspring of women with selected HHD have an excess risk of CCM, the authors examined data from a nationwide birth defects monitoring program (BDMP) covering about 2.9 million births in the United States between 1982 and 1988. The system ascertains major birth defects diagnosed in the newborn period. An anonymous linkage procedure linked maternal obstetric records with newborn records using demographic, diagnostic, and geographic variables. A total of 1,239 mothers were identified with selected HHD (47 hereditary spherocytosis, 575 thalassemias, 310 sickle cell anemia, 88 other hereditary hemolytic anemias, 159 von Willebrand disease, and 60 other congenital coagulapathies). In all, 14 infants received a newborn discharge diagnosis of CCM (expected number based on population rates of CCM from the same hospitals and time period is 7.74;P= 0.0268). No single CCM entity accounted for this excess. In contrast, 8 infants had major non‐CCM defects (expected number 7.46;P= 0.466). These data suggest an excess risk of CCM among offspring of women with selected HHD. Further studies are needed to explore these findings and to evaluate the pathogenetic significance of this associatio

ISSN:0741-0395    

DOI:10.1002/gepi.1370080608

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

年代:1991

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370080609

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

年代:1991

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370080601

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

年代:1991

数据来源: WILEY