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Biomedical subjects

D C Rao

Publications and source records attributed to D C Rao.

At least 19 recordsLinked to original sources
PubMed1992

Commingling and complex segregation analysis of fasting plasma glucose in the Lipid Research Clinics family study.

Commingling and segregation patterns of fasting plasma glucose (GL) were examined in family data from 5 clinics (Cincinnati, Stanford, Iowa, Minnesota, and Oklahoma) of the Lipid Research Clinics (LRC) family study. In addition to the primary question of whether there was a major gene for GL, a secondary purpose was to investigate the possibility of genetic heterogeneity among the 5 clinics. No statistical support was found for heterogeneity among clinics, either in the commingling of distributions or in the segregation patterns. For the combined clinics sample, both a major effect and a multifactorial component were significant. However, the major effect (accounting for 73% of the variance) was not found to be consistent with a major gene, as the hypothesis of Mendelian transmission was rejected. The most parsimonious model involved equal transmission probabilities, which suggests that the major effect is not transmitted from parents to offspring. Possible sources of this major non-Mendelian effect were explored. The multifactorial component accounted for 10% of the variance in GL levels, and no generational differences were noted. Although our study was unable to provide evidence in favor of a major gene effect, it should be noted that a major gene cannot be firmly refuted. For example, a variety of interactions, such as genotype-dependent age effects, could have masked the transmission probabilities.

Adolescent↗
PubMed1992

Family study of alpha 1-antitrypsin deficiency: effects of cigarette smoking, measured genotype, and their interaction on pulmonary function and biochemical traits.

To gain insight into the variable expression of lung disease in alpha 1-antitrypsin (alpha 1AT) deficiency, five quantitative variables including forced expiratory volume at 1 sec (FEV1), forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25-75), total serum alpha 1AT, oxidized serum alpha 1AT, and total serum immunoglobulin E (IgE) were measured in alpha 1AT deficient individuals and their families. The effect of a known, measured genotype (the Pi type) was estimated for each quantitative trait; the influence of mode of case ascertainment on the measured genotype effect was also assessed. These analyses showed that total alpha 1AT levels are strongly influenced by Pi type; IgE levels are unaffected by Pi type; and FEV1, FEF25-75, and oxidized alpha 1AT are moderately influenced by Pi type. The effect of genotype-by-environment interaction between Pi type and pack-years of cigarette smoking on the five quantitative phenotypes was studied using an analysis of covariance. Significant Pi x pack-years interaction was evident for FEV1, but this effect is confounded in this data set with the Pi x age interaction. Probands who were ascertained because they had chronic obstructive pulmonary disease (COPD) do not demonstrate the significant Pi x pack-years interaction effect of the Pi x pack-years subjects ascertained for other reasons demonstrate. The effect of the Pi x pack-years interaction on FEV1 was no longer significant on a transformed scale, (FEVf12,) thus providing an additive scale for future data analysis. The increased sensitivity of Pi MZ individuals in our sample to cigarette smoking reduced the Pi x packs-years interaction effect on FEF25-75 to borderline significance. This investigation has provided an opportunity to incorporate both measured genotype and genotype-by-environment interaction analyses into the study of the variable expression of lung disease in Pi Z individuals.

Family↗
PubMed1992

Commingling analysis of regional fat distribution measures: the Québec family study.

Regional fat distribution is related to higher risk of diabetes and cardiovascular morbidity and mortality, independent of excess body mass for height. In particular, the male (android) pattern of fat deposition, which is characterized by greater truncal and abdominal fat stores relative to extremity fat levels, is associated with a higher propensity to metabolic complications. Motivated by these considerations, we have initiated a systematic investigation of several measures of regional fat distribution aimed at the detection of possible single gene effects. In this paper, we assess the evidence for commingling in the distributions of these variables in a large French-Canadian study. Two measures approximating the size of subcutaneous fat stores relative to total body fat were considered: the sum of six skinfolds (SF6 = abdominal + supra-iliac + subscapular + calf + tricep + bicep), and the sum of three trunk skinfolds (TSF3 = abdominal + supra-iliac + subscapular). In addition, two measures assessing the distributional pattern of subcutaneous fat were considered: the ratio of TSF3 to the sum of the three extremity skinfolds (TER), and a relative fat pattern index [RFPI = subscapular/(subscapular + supra-iliac)]. All four measures were assessed both prior to and after adjusting for total fat mass, which was measured using underwater weighing. Significant distributional heterogeneity was observed for some of these measures, either between generations and/or between the sexes. In general, however, fat mass adjustment tended to eliminate the heterogeneity; the exception was for RFPI, for which sex differences were noted both prior to and after the adjustment. The finding of commingling of distributions for almost all phenotypes is consistent with (but not evidence for) major gene effects. However, for some of the measures the effect of a putative major locus genotype may be mediated by covariates such as age and/or sex.

Adipose Tissue↗
PubMed1992

Familial resemblance of blood pressure with residual household environmental effects in consanguineous and nonconsanguineous families from Andhra Pradesh, India.

Familial aggregation of blood pressure (BP), both systolic (SBP) and diastolic (DBP), was examined in consanguineous and nonconsanguineous families from southern India. Path analysis of BP suggests inbreeding effects, with the genetic variance for SBP being lower in the sample that included inbred families. Specifically, genetic heritability for SBP was 38% in the nonconsanguineous sample but only 23% in the combined sample. Genetic heritability for DBP (30%) did not vary by sample, nor were sample differences in cultural heritability detected for either SBP (over 35%) or DBP (about 18%). These findings are remarkably similar to those in a French-Canadian population of Quebec; both reports found a considerably larger effect of the home environment on BP than previous studies.

Blood Pressure↗
PubMed1991

Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Stanford Lipid Research Clinics Family Study.

We examined the familial aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] in families ascertained through random and nonrandom probands in the Stanford Lipid Research Clinics Family Study. Nonrandom probands were selected because their lipid levels at a prior screening visit exceeded a certain prespecified threshold. The statistical method is based on selection through indirect truncation on a correlated trait (in which the likelihood function is conditioned on the actual event that the proband's value is beyond the threshold). This method allows for estimation of the path model parameters in randomly and nonrandomly ascertained families jointly and separately, thus enabling tests of heterogeneity between the two types of samples. The results suggest that the multifactorial transmission is homogeneous in the random and hyperlipidemic samples for CH. However, the evidence for heterogeneity is moderate for LDL, marked HDL, and mixed for TG. The general pattern of observed results is for somewhat higher genetic heritabilities in the random than nonrandom samples, which is compatible with a higher prevalence in the random sample of certain dyslipoproteinemias associated with nonelevated lipids. Substantial genetic heritability is found for CH, HDL, and LDL, with somewhat lower estimates for TG. Cultural heritability is low but significant for all four traits. Little or no spouse resemblance or nontransmitted shared sibship effects are seen. In contrast to the findings from previous studies, little or no parental cultural transmission is seen.

Adult↗
PubMed1991

Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Iowa Lipid Research Clinics family study.

The aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] in families ascertained through random and nonrandom probands in the Iowa Lipid Research Clinics family study was examined. Nonrandom probands were selected because their lipid levels (at a prior screening visit) exceeded a certain pre-specified threshold. The statistical method conditions the likelihood function on the actual event that the proband's value is beyond the threshold. This method allows for estimation of the path model parameters in randomly and nonrandomly ascertained families jointly and separately, thus enabling tests of heterogeneity between the two types of samples. Marked heterogeneity between the random and the hyperlipidemic samples is detected in the multifactorial transmission for TG and HDL, and moderate heterogeneity is detected for CH and LDL, with a pattern of higher genetic heritability estimates in the random than nonrandom samples. The observed pattern of heterogeneity is compatible with a higher prevalence in the random sample of certain dyslipoproteinemias that are associated with nonelevated lipids. For the random samples, genetic heritabilities are higher for CH and HDL (about 60%) than for TG and LDL (about 50%). For the nonrandom samples those estimates are about 45, 40, 35 and 30% for HDL, CH, LDL and TG, respectively. Little to no cultural (familial environmental) heritability is evident for CH and LDL, although 10-20% of the phenotypic variance is due to cultural factors for TG and HDL. These results suggest that the etiologies for lipids and lipoproteins may be quite different in random versus hyperlipidemic samples.

Adult↗
PubMed1991

Commingling analysis of generalized body mass and composition measures: the Québec Family Study.

Human body mass and composition are heterogeneous phenotypes resulting from the combined effects of genes, environmental factors, and their interactions. In order to gain an understanding of the individual genetic determinants leading to obesity, we have initiated a systematic analysis of several measures of fatness and its phenotypes including: the body mass index (wt/ht2), fat mass, fat-free (lean) mass, the ratio of fat mass over fat-free mass, percent body fat, and a fat mass index (fat mass/ht). In this report, we examine the distributions of these age and sex adjusted variables in a large family study from Québec in terms of evidence for commingling and skewness, and evaluate the inter-relationships among the measures. Fat mass, fat-free mass and the fat mass index conceptually represent primary variables in that they are quantitative measures of relevant components of total body weight; the hypothesis of a single distribution was inferred for each of these primary measures, with significant residual skewness except for fat mass. In general, offspring (8-26 years old) distributions were more positively skewed than parent (30-60 years old) distributions. The remaining variables (body mass index, fat mass to fat-free mass ratio, and percent body fat) are indexes combining information on fat and fat-free mass into single measures. Although offspring data were consistent with a single skewed distribution, commingling was found in the parents in each case. The prominent heterogeneity between generations suggests that there may be significant developmental (genetic or environmental) effects in the transition during growing years to adult pattern phenotypes, particularly for the complex indicators of body composition.

Adipose Tissue↗
PubMed1979

Genetic and environmental determinants of periodontal disease.

Reanalysis of data on periodontal disease in 241 families [Chung et al, 1977b], based on an extended and more satisfactory path model [Rao et al, 1979], failed to detect significant heritability, and concluded in favor of cultural inheritance only, without maternal effects or intergenerational differences. The most parsimonious hypothesis yields a relative variance component of 0.338 +/- 0.024 due to indexed environment for both children and adults, the remainder (1.0--0.338 = 0.662) being due to residual nongenetic factors.

Culture↗
PubMed1979

Determinants of plasma uric acid.

Obesity, alcohol consumption, and hematocrit provide an index of plasma uric acid, which in path analysis has a cultural heritability of 0.11 in children and 0.23 in parents, a small maternal effect, and a genetic heritability of 0.25 in both generations. Preliminary evidence for a major locus is destroyed by the omission of one exceptional child. There is no evidence against the polygenic hypothesis for hyperuricemia in the Japanese-American population studied.

Adult↗
PubMed1979

Cultural and biological determinants of lipoprotein concentrations.

A general linear model is presented here for biological and cultural inheritance involving ten parameters to be estimated from 16 correlations in nuclear families, providing ample degrees of freedom to test goodness of fit. Applied to six lipoprotein traits the model fits acceptably to all, although there is evidence of transient maternal effects for cholesterol and lipemia. Genetic heritability in children ranges from 0.175 for triglyceride to 0.562 for total cholesterol. Cultural heritability in children ranges from 0.012 for VLDL to 0.149 for HDL-cholesterol.

Adult↗
PubMed1979

Complex segregation analysis of diabetes mellitus.

Complex segregation analysis was applied to a sample of 12,293 nuclear families each with at least 1 diabetic patient. The families were divided into two groups depending on the proband's treatment: insulin-dependent (IDG) and insulin-independent (IIG). Heterogeneity analysis has revealed a highly significant difference in the IIG group when families were divided into different mating types. The higher recurrence risk was found in the group with affected mothers. Also evidence for a major recessive gene was found in the IGG group, while it was not possible to distinguish between the hypothesis for absence of a major locus and absence of polygenic inheritance in the IDG group. Risks to develop the disease were calculated for a few typical situations.

Adolescent↗
PubMed1979

Joint distribution of z transformations estimated from the same sample.

When correlations are estimated by maximum likelihood method from the same sample, Fisher's z transformations of the correlations (as well as the sample correlations themselves) are shown to be asymptotically distributed as multivariate normal with appropriate mean and dispersion matrix.

Genetics, Population↗
PubMed1979

A maximum likelihood map of chromosome 1.

Thirteen loci are mapped on chromosome 1 from genetic evidence. The maximum likelihood map presented permits confirmation that Scianna (SC) and a fourteenth locus, phenylketonuria (PKU), are on chromosome 1, although the location of the latter on the PGM1-AMY segment is uncertain. Eight other controversial genetic assignments are rejected, providing a practical demonstration of the resolution which maximum likelihood theory brings to mapping.

Chromosome Mapping↗