Identification of an insulin receptor exon 8 NsiI polymorphism using the polymerase chain reaction.
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Chromosomes, Human, Pair 19↗
Biomedical subjects
C L Hanis
Publications and source records attributed to C L Hanis.
Genetics and public health in the 1990s.
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Forecasting↗
Diabetes, gallbladder disease, obesity, and hypertension among Hispanics in New Mexico.
Because Hispanics in the Southwest are genetically admixed with American Indians, the hypothesis has been advanced that the excess occurrence of diabetes mellitus, obesity, and gallbladder disease in this ethnic group may be genetic in origin and results from genes derived from American Indians. This report describes the prevalence of these diseases in 1,175 adult Hispanic participants in a survey of a New Mexico community conducted in 1984-1985. At nearly all ages, the majority of subjects had a body mass index of 25 kg/m2 or greater, and a substantial proportion exceeded 30 kg/m2. The prevalence of obesity was much greater in these Hispanics than is shown in nationwide data for US whites. Diabetes mellitus was also reported more often by Hispanic subjects in this survey than by US whites nationwide. A report of gallbladder trouble or of gallbladder removal was common in both males and females; the prevalence of gallbladder removal was as high in this population as in Mexican Americans previously studied in Starr County, Texas. In spite of the high prevalence of obesity, hypertension was less frequent among the New Mexico Hispanics than is shown in nationwide data for US whites. These findings complement those of previous surveys in Texas, which have shown a notably high proportion of adults to be obese, to have non-insulin-dependent diabetes mellitus, and to have gallbladder disease. The similar epidemiology of these diseases in the Hispanics of New Mexico and the Mexican Americans of Texas supports the hypothesis that American Indian admixture underlies the development of these conditions in Hispanics throughout the Southwest.
Adolescent↗
Nonrandom sampling in human genetics: skewness and kurtosis.
When a multivariate normal sample is chosen from a truncated space of one of its components one can no longer make use of the normality assumption for the sample observations or for the estimates derived from them. In this paper, skewness and kurtosis for each component are derived analytically under a broad class of nonrandom sampling. It is shown that the distortions in skewness and kurtosis produced by nonrandomness are negligible, except those for the component with respect to which the selection of sampling regions is based. The usual tests of normality from sample values of skewness and kurtosis measures remain valid under nonrandom sampling, except for the selection variable. The implications of these analytical results in the context of commingling analysis in genetic epidemiology are discussed. It is recommended that when samples of families are obtained through nonrandomly ascertained probands, a commingling analysis should treat each relative class separately, since such analyses based on the pooled sample of individuals may involve unspecified bias in the levels of the test procedure.
Genetics, Medical↗
Centralized obesity and cardiovascular disease risk in Mexican Americans.
The association between body fat distribution patterns and cardiovascular disease risk variables (high density lipoprotein (HDL) cholesterol, total cholesterol, diastolic and systolic blood pressures, and fasting blood glucose levels) was sought in a sample of Mexican American adults who were studied during 1981-1983 in Starr County, Texas. In the sample, all diabetics were excluded to see whether centralized obesity carried any risk for cardiovascular disease independent of diabetes. A component of centralized body fat distribution was identified through the use of principal components analysis of five skinfold measurements, which included the upper and lower extremities and trunk areas. The centralized obese were compared with generalized (peripheral) obese and nonobese controls in four subgroups of the population: younger and older adult males and females. The means of all cardiovascular risk variables were in a direction indicating that the centralized obese were significantly at greater risk than nonobese controls (in particular, HDL cholesterol, total cholesterol, and blood glucose levels). The generalized obese differed from the centralized obese in having significantly lower blood glucose levels, and tended to be intermediate between centralized obese and nonobese controls in the other variables. The data confirm that centralized obesity as defined by a linear combination of skinfold measures works in the same way as the waist-to-hip circumference ratio in describing a body build factor which heightens the risk of cardiovascular disease in the obese independent of the clinical diabetic state.
Adult↗
Body circumferences as alternatives to skinfold measurements of body fat distribution in Mexican-Americans.
The ratios of circumferences (waist/hip, waist/thigh) have been proposed in lieu of skinfold measurements for studies of obesity and body fat distribution. The purpose of this paper is to present our experience in measuring a series of body circumferences and skinfolds in an obese population, and seek the relationship between these two kinds of variables as indicators of fatness and body fat distribution using canonical correlation analysis. With this method, weighted vectors of circumferences on the one hand and skinfolds on the other, are formed in such a way that the correlation between the two sets of variables is maximized. The weights (regression coefficients) and their signs help us select the best combination of circumferences which describe a component of centralized obesity. Our experience showed that 21 percent of women would have been excluded from this multivariate analysis due to skinfolds what could not be measured (mainly due to poor fold definition). Few men were so excluded (6 per cent), and almost all circumferences could be measured in both sexes. A first canonical correlation was substantial (0.84 in women, 0.89 in men) and appeared to relate to level of fatness. A second canonical correlation was moderate (0.59 in women, 0.42 in men) and statistically significant (P less than 0.01) in both sexes. Only in women was it independent of age, but in both sexes it reflected differences in central and peripheral (especially lower limb) fat. The simple waist/thigh ratio correlated well with the second canonical variate (0.79 in women, 0.67 in men).(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Individual admixture estimates: disease associations and individual risk of diabetes and gallbladder disease among Mexican-Americans in Starr County, Texas.
The ethnic and geographic distributions of several common chronic diseases show distinct patterns that are consistent with the distribution of genes and genetic admixture. For example, diabetes and gallbladder disease occur most frequently among Amerindians, while those genetically admixed with them (such as Mexican-Americans) have intermediate rates, and lowest rates are found among Whites and Blacks. Because there will be heterogeneity from individual to individual in ancestral affinity within an admixed population, a method is developed for estimating each person's admixture probability. Results confirm that there is substantial heterogeneity of individual admixture among Mexican-Americans in Starr County, Texas, with a mean value indicating that 65% of genes in this population are Caucasian derived and 35% Amerindian derived. The individual estimates are shown to be unrelated to the probability of being diabetic and only marginally related to gallbladder disease, with those having the most Amerindian affinity being at increased risk. These results are a consequence of the independent assortment of loci and indicate that unless the markers employed are related (including linkage) to the disease of interest, the method will have limited utility. Individual admixture estimates will be useful, however, for examining aspects of population structure and will find increased utility for predicting disease and examining disease associations as more and more of the genome is represented by markers, a very probable prospect with the abundance of DNA polymorphism being identified by restriction enzymes.
Adolescent↗
How much of variability in apolipoprotein AII concentrations is explained by polymorphism adjacent to apo-AII gene?
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Apolipoprotein A-II↗
Hypertension and sources of blood pressure variability among Mexican-Americans in Starr County, Texas.
Previous investigations have established that the Mexican-American community of south Texas has a three- to five-fold elevated risk for non-insulin dependent diabetes mellitus when compared to the US population as a whole. In addition, evidence points to similarly increased risks of the related disorders, hypertension and obesity. In this paper, age- and sex-specific rates of borderline and definite hypertension among 1931 Mexican-Americans aged 15 years and above based on a single, at-home blood pressure determination are reported. Observed rates of definite hypertension are uniformly lower than the US population while borderline hypertension is correspondingly higher for all age and sex strata yielding overall prevalences of hypertension which are not significantly different. The Starr sample, however, has one and one-third times as many individuals taking hypertensive medications so that the true rate of hypertension is likely to be higher. Examining sources of blood pressure variability using analyses of covariance indicate that age has the most significant effect. A direct measure of body size was not available, but classification based on simple silhouettes representing body form is shown to be the next most significant effect. Furthermore, the silhouettes appear to provide nearly an equivalent amount of information as does the body mass index as an empirical predictor of blood pressure variability. Diabetic classification is a significant effect for systolic blood pressure in females, but not for males or for diastolic pressure in either.
Adolescent↗
Gallbladder disease epidemiology in Mexican Americans in Starr County, Texas.
The prevalence of gallbladder disease (surgery or complaints) among Mexican Americans in Starr County, Texas, is demonstrated to be some threefold higher than in Framingham, with 13% and 26% of males and females, respectively, over the age of 35 years having the disease. The population aggregation of gallbladder disease in Amerindian groups and those genetically admixed with them (as the present case) is consistent with an underlying genetic mechanism which is further substantiated here by examining relative risks in sibs, offspring, and spouses of individuals with gallbladder disease. It is shown that in females under the age of 45 years, there is evidence for a significant association between gallbladder disease and diabetes beyond that which could be explained by body mass. Significant gallbladder disease by nonlinear age interaction effects was detected for serum cholesterol. The predicted regression lines of cholesterol by age were uniformly lower for individuals with gallbladder disease than those without it except for ages 40-55 years, in which the lines were equal. When coupled with previous results on diabetes, the results presented document the extent to which diabetes and gallbladder disease dominate the health status of Mexican Americans in southern Texas and likely elsewhere.
Adolescent↗
The Diabetes Alert study: growth, fatness, and fat patterning, adolescence through adulthood in Mexican Americans.
Diabetes Alert is a multidisciplinary genetic and epidemiological study of Type II (non insulin-dependent) diabetes in Texas Mexican Americans. We report the anthropometry of 1,155 individuals 10 to 70 or more years with particular reference to overweight, fatness, and anatomical fat patterning in the sample. Children ages 10-18 of both sexes are growing at the 50th percentile of the reference data (U.S. Health and Nutrition Examination Survey-1) for height, Wt/Ht2, and triceps and subscapular skinfolds. Adults are well below median height but well above median Wt/Ht2 and skinfolds. Prevalence of obesity (Wt/Ht2 greater than or equal to 30) among adults is typically 30% or higher by age 30. Diabetics compared to age/sex-matched non diabetics have shorter sitting heights, have more upper body fat (subscapular skinfold), have less lower body fat (lateral calf skinfold), and were heavier at maximum weight and at age 18. The ratio of lower to upper body fat distribution decreases over the life cycle, being highest at adolescence and lowest at ages 40-50 in both sexes. Our results show a precipitous weight gain after maturity in the sample and an association of diabetes with differences in anatomical fat patterning. The age-related changes in fat patterning need to be explained in terms of their ecological and genetic influences.
Adipose Tissue↗
Nonrandom sampling in human genetics: familial correlations.
In the context of human genetics, sampling is often nonrandom in that pedigrees are frequently selected by virtue of their having at least one affected individual. For quantitative traits, it may be that the proband is selected because of a phenotypic value above some predetermined cut-point; this will also be true for diseases defined by a cut-point above which individuals are said to be affected (e.g. diabetes, hypertension, and obesity). Relatively little attention has been given to the implications of these forms of nonrandom sampling. In this paper, we show that the biases introduced by such sampling are sufficient to lead to erroneous model specification and biased parameter estimates in path analysis. Existing methodologies used to correct for such sampling (e.g., elimination of proband or regression techniques) also result in similar bias in estimation and model fitting. Thus, it is possible to make inferences which do not reflect underlying biology, but are artifacts of the sampling design. As a consequence, method-of-moment estimators are developed for means, variances, and correlations under such sampling. Simulation results are used to demonstrate the superiority of this method over alternate strategies.
Biometry↗
Glycosylated hemoglobin determination from capillary blood samples. Utility in an epidemiologic survey of diabetes.
Total glycosylated hemoglobin was measured from capillary blood specimens obtained from a sample of 1880 individuals of Mexican-American ancestry residing in Starr County, Texas, between January 1981 and February 1982, as part of an epidemiologic survey to assess the prevalence of noninsulin-dependent diabetes mellitus (Type II). No significant difference was found between males and females. Diabetics were found to have significantly higher levels of glycosylated hemoglobin than nondiabetics. However, among diabetics, there was no significant difference between newly diagnosed and known diabetics, and known diabetics taking medication did not differ significantly from those not taking medication. An analysis of the specificity and sensitivity of glycosylated hemoglobin, fasting blood glucose, and casual blood glucose determinations as screening devices in a survey of diabetes prevalence reveals that glycosylated hemoglobin is superior to casual blood glucose determination. The conditions under which various screening devices might be more effective are discussed.
Diabetes Mellitus, Type 2↗
Genetics and epidemiology of gallbladder disease in New World native peoples.
Native peoples of the New World, including Amerindians and admixed Latin Americans such as Mexican-Americans, are highly susceptible to diseases of the gallbladder. These include cholesterol cholelithiasis (gallstones) and its complications, as well as cancer of the gallbladder. Although there is clearly some necessary dietary or other environmental risk factor involved, the pattern of disease prevalence is geographically associated with the distribution of genes of aboriginal Amerindian origin, and levels of risk generally correspond to the degree of Amerindian admixture. This pattern differs from that generally associated with Westernization, which suggests a gene-environment interaction, and that within an admixed population there is a subset whose risk is underestimated when admixture is ignored. The risk that an individual of a susceptible New World genotype will undergo a cholecystectomy by age 85 can approach 40% in Mexican-American females, and their risk of gallbladder cancer can reach several percent. These are heretofore unrecognized levels of risk, especially of the latter, because previous studies have not accounted for admixture or for the loss of at-risk individuals due to cholecystectomy. A genetic susceptibility may, thus, be as "carcinogenic" in New World peoples as any known major environmental exposure; yet, while the risk has a genetic basis, its expression as gallbladder cancer is so delayed as to lead only very rarely to multiply-affected families. Estimates in this paper are derived in part from two studies of Mexican-Americans in Starr County and Laredo, Texas.
Adolescent↗
Implications of nonrandom sampling in genetic epidemiology.
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Genetics, Medical↗
Diabetes among Mexican Americans in Starr County, Texas.
An increasing body of evidence suggests that diabetes mellitus constitutes a major health burden among the Mexican-American population. For example, county-wide death rates in Texas attributable to diabetes from 1970-1981 range from 2.5-52.0 diabetes deaths per 1000 total deaths with the highest rates generally occurring in counties whose populations are more than 75% Spanish ancestry. To assess the prevalence and morbidity of noninsulin-dependent diabetes mellitus among Mexican Americans, 14% of the Starr County, Texas, population (97% Mexican-American) was randomly sampled. The reference population, sampling strategy, and screening results are described. Age-specific prevalences of diabetes for males ranged from 0% in males aged 15-24 years to 17.6% in those above 75 years of age. Rates for females ranged from 0.4% in those aged 15-24 years to a high of 19.0% in the 55- to 64-year age group. In both sexes, the rates are relatively low for persons under age 45 with a sharp increase in those aged 45-54 years and high rates prevailing in the older age groups. Comparisons of the rates in Starr County to those of the general US population indicate a two- to fivefold greater risk in Starr County. In terms of impact on this community, these results imply that over 50% of individuals older than 35 years are directly affected by diabetes by virtue of their having the disease or by being a first-degree relative of a diabetic.
Adolescent↗
Multivariate models for human genetic analysis: aggregation, coaggregation, and tracking of systolic blood pressure and weight.
A multivariate path model parameterizing the sources of familial aggregation and coaggregation of systolic blood pressure and weight, as well as their tracking across time, is applied to longitudinal data collected in Muscatine, Iowa. Genetic, common household, and individual environmental effects, pleiotropy, and a direct regression effect of blood pressure on weight are parameterized. The sample consisted of 998 individuals distributed in 261 families of whom 601 were measured on four successive occasions. The data were divided with times 1 and 2 forming group 1, and times 3 and 4, group 2. Model fitting and estimation was performed using group 1, followed by testing the model and estimates using the data in group 2. Heritability estimates for systolic blood pressure and weight were .15 and .54, respectively. The genetic correlation between these traits was nonsignificant, but there was a significant direct regression effect. The results indicate that 30% of the full-sib correlation for systolic blood pressure is attributable to the aggregation of weight. In terms of tracking, 59% and 60% of the predicted systolic blood pressure and weight correlations, respectively, were attributable to genetic effects. Testing the model from group 1 in group 2 indicates that the qualitative relationships between blood pressure and weight are stable with time.
Adolescent↗
Non-random sampling in human genetics: estimation of familial correlations, model testing, and interpretation.
By choice or necessity, human geneticists and genetic epidemiologists often design studies that involve non-random sampling of clusters of individuals, and yet address hypotheses appropriate to the population as a whole. Failure to adjust for the non-randomness of data often leads to biased parameter estimates and misspecification of predictive models that cause familial resemblance of traits. We develop an approach to adjust for common forms of non-randomness in the context of estimating familial correlation with minimal distributional assumptions and discuss its implications in connection with adjustments for concomitant variables.
Analysis of Variance↗