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T H Beaty

Publications and source records attributed to T H Beaty.

At least 127 records · Page 7Linked to original sources
PubMed1987

Robust inference for variance components models in families ascertained through probands: I. Conditioning on proband's phenotype.

A robust approach for estimating standard errors of variance components by using quantitative phenotypes from families ascertained through a proband with an extreme phenotypic value is presented. Estimators that use the multivariate normal distribution as a "working likelihood" are obtained by computing conditional ln-likelihoods, conditional first and second derivatives in a Newton-Raphson approach. Robust estimates of standard errors about the estimators are also provided. Tests of hypotheses are based on a modification of the score test, which allows the assumption of multivariate normality to be relaxed. Conditional goodness-of-fit statistics are proposed that can be used to examine the fit of separate pedigrees to the overall model. This robust approach for estimating the standard errors for variance components by conditioning on the proband's phenotype will allow general inferences to be made from the analysis of families ascertained through probands with extreme or unusual phenotypes and should be most appropriate for studying many physiological traits that may be intrinsically nonnormal.

Analysis of Variance↗
PubMed1987

Robust inference for variance components models in families ascertained through probands: II. Analysis of spirometric measures.

Three spirometric measures of pulmonary function were used to estimate genetic and nongenetic components of variance for 781 members of 158 families ascertained through a proband with obstructive pulmonary disease. Forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and the ratio of these two (FEV1/FVC) were adjusted for age, sex, race, smoking, and height and used in a robust approach to estimate variance components after conditioning on the proband's observed value. The best fitting model for both residual FEV1/FVC and FEV1 included an additive genetic component representing 25% and 9% of the variation in these two traits, respectively. In addition, there was a significant correlation between parents in residual FEV1/FVC, and a component shared among full sibs was statistically significant for residual FEV1. No evidence of a genetic component for residual FVC was found in this analysis. Although these results agree with previous reports based on other populations in showing a substantial degree of direct genetic control over spirometric measures of pulmonary function, they also raise the possibility of etiologic heterogeneity.

Analysis of Variance↗
PubMed1987

Multipoint mapping studies of six loci on chromosome 11.

The six loci, beta-globin (HBBC), parathyroid hormone (PTH), oncogene c-Ha-ras-1 (HRAS1), insulin (INS), calcitonin (CAL) and catalase (CAT) loci, have been mapped to 11p in the order: CAT-CAL-PTH-HBBC-(HRAS1-INS). The purpose of the current study was to examine the linkage relationships, especially the multipoint relationships of these loci in detail. In the 18 families studied, a significant sex difference in recombination was found for the HBBC: HRAS1 linkage with more recombination in the male parent than the female parent (22 vs. 2%). The results of the multipoint analyses provided further evidence for the order CAT-CAL-PTH-HBBC-(HRAS1-INS); however, the order of the last two tightly linked loci is still not clear.

Calcitonin↗
PubMed1987

Genetic analysis of juvenile periodontitis in families ascertained through an affected proband.

Data from 28 families ascertained through a proband with juvenile periodontitis were used to test a series of Mendelian models of inheritance that included both autosomal and X-linked transmission. There was strong evidence of familial aggregation of this progressive dental disease, and the best-fitting model was an autosomal recessive model. Because of the rather limited age range for expression of the disease in this situation, simulations were done, in a model-choice analysis using samples of this size, to assess the chance of mistaking an autosomal dominant disease (with masking of the affected phenotype outside a specified age range) for an autosomal recessive disease. While the rate of Type II error was fairly high (40%) when competing models in these simulations were compared, these data suggest that it is reasonable to infer that juvenile periodontitis is an autosomal recessive disorder.

Adolescent↗
PubMed1987

Inheritance of total serum IgE (basal levels) in man.

Since allergic individuals with atopic allergy tend to have higher total serum IgE levels than do nonallergic subjects, family studies of total serum IgE levels are necessary in delineating the genetic and environmental factors involved in the expression of allergic disease. However, previous studies do not agree as to the genetic basis of total IgE production. To try to resolve this conflict, a total of 278 individuals from 42 nuclear families ascertained for large family size (at least four children) were studied. The families were not selected for the presence of allergic disease. Segregation analysis showed that the mixed model of recessive inheritance of high levels was most appropriate for these data--with approximately 36% of the total phenotypic variation in log[IgE] attributable to genetic factors, equally divided between a Mendelian component and a more general polygenic component. Thus, these data suggest some role for Mendelian control of basal IgE levels, but there is significant familial aggregation in IgE levels over and above that due to a Mendelian factor.

Analysis of Variance↗
PubMed1986

Problems in detecting etiological heterogeneity in genetic disease illustrated with retinitis pigmentosa.

Simulated data were generated under four etiologic mechanisms for each of 20 different pedigree structures drawn from a study of families ascertained through a proband with retinitis pigmentosa. These simulated data were then used to identify subgroups of pedigrees which best supported each of three genetic mechanisms (autosomal dominant, autosomal recessive, X-linked recessive with 10% penetrance of disease in heterozygous females) and a non-genetic, sporadic mechanism. Results of these studies show that pedigrees identified as supporting one genetic model in a 'model choice' approach tend to be etiologically homogeneous, but are not truly representative of all the phenotypic combinations possible under that mechanism. The problem of etiologic heterogeneity is most acute when dealing with pedigrees less than size 10. Pedigrees lumped under a non-genetic, sporadic mechanism are extremely heterogeneous and studies of the natural history of diseases where both genetic and non-genetic mechanisms may be operating (such as with retinitis pigmentosa) should avoid using this group of largely simplex pedigrees.

Female↗
PubMed1986

Interaction of genetics and epidemiology in the literature.

To evaluate the extent of interaction between genetics and epidemiology in studies reported in the literature, we reviewed all the "familial/genetic" papers published in a standard epidemiology journal (American Journal of Epidemiology, AJE) and all the "epidemiology" papers published in a standard human genetics journal (American Journal of Human Genetics, AJHG) between 1966 and 1984. A variety of medline subject headings were used in this search. Computerized listings of titles, subject headings, and abstracts were reviewed. It could be shown that familial/genetic papers constituted 4.3% of all papers published in AJE and epidemiology papers constituted 16.4% of papers published in AJHG. Over time, familial/genetic studies published in AJE increased both in number and in proportion of all papers, and more family studies are using complex statistical genetic techniques. On the other hand, epidemiology papers published in AJHG did not increase in number over time, and actually decreased in relation to all papers. These papers were mostly either descriptive (eg, defining frequencies of Mendelian traits in populations) or analytical (eg, defining risk factors for chromosomal abnormalities, and other reproductive outcomes). This analysis suggests that epidemiologic methods have been widely used in the genetic literature, and that genetic methods are gaining more access to the recent epidemiology literature. Because of increasing recognition of the role of genetic factors in disease, there is a growing need to incorporate both genetic and epidemiologic methods in etiologic studies of complex disorders.

Epidemiology↗
PubMed1986

Genetic-environmental interactions in chronic airways obstruction.

To examine patterns of interaction between cigarette smoking and genetic factors in relation to airways obstruction, cross sectional data were analysed on 1787 white non-patient adult participants in a genetic-epidemiological study of airways obstruction (AO), defined as one-second forced expiratory volume FEV1 less than 68% of forced vital capacity FVC. Interaction was examined between smoking and each of four factors previously found to be related to AO: alpha-1 antitrypsin (PiZ allele), ABO blood groups (A antigen), ABH non-secretor status, and first degree relationship to a COPD or lung cancer patient. Multiple linear regression was used to test for interaction and adjust mean FEV1 (as a per cent of FVC) and prevalence of AO for age, sex, socioeconomic status, coffee and alcohol intake. Statistical interaction was observed between smoking (measured in pack-years) and two genetic factors (presence of blood A antigen and the family history). At higher pack-year levels, those individuals with the A antigen or the family history, but especially those with both factors had a much lower mean FEV1/FVC % and a much higher prevalence of AO than expected based on a simple additive model. On the other hand, there was no interaction between smoking and PiZ allele, or smoking and ABH secretor status. The findings suggest a possible biological interaction between cigarette smoke and the airways of individuals with blood group A antigen and familial lung disease. The findings also emphasize the role of genetic-environmental interactions in chronic diseases of multifactorial aetiology.

ABO Blood-Group System↗
PubMed1986

Application of odds ratio regression models for assessing familial aggregation from case-control studies.

A regression model for estimating covariate effects on odds ratios to test for familial aggregation of common disease in first-degree relatives of cases and controls is presented and illustrated by using family data from a study of chronic obstructive pulmonary disease. These estimators are in essence an extension of the Mantel-Haenszel estimator of odds ratio but do not require the assumption of independence among relatives. A robust test statistic for possible effects of covariates such as the matching variables for cases and controls on odds ratio is also presented. In data on 156 adult first-degree relatives of 28 cases with demonstrated airway obstruction and 28 controls matched for age, sex, race, and hospital status, there appeared to be a difference in the odds ratio among families of black and white case-control pairs. However, the small sample size available prevents conclusive interpretation of this observation.

Adult↗
PubMed1986

Evidence that autoimmunity in man is a Mendelian dominant trait.

Family studies of autoimmune diseases are consistent with multifactorial etiology. However, familial occurrence of the autoimmune trait as defined by the presence of autoimmune disease and/or high titer autoantibody supports the hypothesis that autoimmunity is inherited as an autosomal dominant trait. Based on genetic analysis of 18 autoimmune kindreds, the population frequency of this primary autoimmune gene is approximately .10 with penetrance estimates of 92% in females and 49% in males. The estimated high penetrance of the autoimmune gene in females suggests that the interacting genetic and/or environmental factors must be numerous or ubiquitous. Sex, age, and specific major histocompatibility complex (MHC) antigens are among the genetic and physiological factors known to influence autoimmunity. A genetic model is proposed that takes these factors into account. Inherent in the hypothesis of a primary autoimmune gene is that it is epistatic to other, secondary, genes that influence the autoimmune phenotype. The genetic model further postulates that the secondary genes, including those of the MHC, confer specificity to the phenotype. The effects of the secondary genes can be modulated by gonadal steroids and, over time, may be abrogated by environmental challenges, such as viral infections.

Autoimmune Diseases↗