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Biomedical subjects

J Blangero

Publications and source records attributed to J Blangero.

172 records · Page 10Linked to original sources

Population structure analysis using polygenic traits: estimation of migration matrices.

Many studies of subdivided populations have attempted to determine the underlying migration rates that generate observed patterns of genetic differentiation. Most previous analyses have yielded only qualitative inferences about migration. In this paper I present a new method for estimating the full migration matrix from information on polygenic trait variation. The method employs multivariate quantitative genetic theory to provide a matrix formulation of the expected covariance structure in multigenerational subdivided populations for which information is available at different points in the life cycle. I develop a restricted maximum likelihood technique (REML) to take account of this additional life-cycle information and to estimate both the migration matrix and the ratio of effective population size to census size. To make the problem computationally tractable, the migration matrix is modeled as a log-linear function of a few covariates, such as subdivision size and geographic distance. I apply the technique to data on dermatoglyphic ridge counts for 1015 individuals of the Jirel population of east Nepal, considering two different age cohorts. In the adult cohort (individuals over 21 years of age) I examine data by both birthplace and residence and for the subadult cohort (under 21 years of age), by birthplace. Results from the REML technique reveal that the best-fitting migration model is a finite island model with an estimated endemicity of 0.730 +/- 0.105 and an estimated ratio of effective size to census size of 0.287 +/- 0.095. Both estimates are reasonable given known demographic data. In addition, Fst values predicted by the migration model are concordant with REML estimates obtained directly from the dermatoglyphic variation.

Adolescent↗

Detection of differential gene flow from patterns of quantitative variation.

A major goal in anthropological genetics is the assessment of the effects of different microevolutionary forces. Harpending and Ward (1982) developed a model that aids in this effort by comparing observed and expected heterozygosity within populations in a local region. The expected heterozygosity within a population is a function of the total heterozygosity of the entire region and the distance of the population from the regional mean centroid of allele frequencies. Greater than average gene flow from an external source will result in a population having greater heterozygosity than expected. Less than average gene flow from an external source will result in a population having less heterozygosity than expected. We extend the Harpending-Ward model to quantitative traits using an equal and additive effects model of inheritance. Here the additive genetic variance within a population is directly proportional to heterozygosity, and its expectation is directly proportional to the genetic distance from the centroid. Under certain assumptions the expectations for phenotypic variances are similar. Observed and expected genetic or phenotypic variance can then be compared to assess the effects of differential external gene flow. When the additive genetic covariance matrix or heritabilities are not known, the phenotypic covariance matrix can be used to provide a conservative application of the model. In addition, we develop new methods for estimation of the genetic relationship matrix (R) from quantitative traits. We apply these models to two data sets: (1) six principal components derived from twenty dermatoglyphic ridge count measures for nine villages in Nepal and (2) ten anthropometric measurements for seven isolated populations in western Ireland. In both cases both the univariate and multivariate analyses provide results that can be directly interpreted in terms of historically known patterns of gene flow.

Anthropology, Physical↗

Familial analysis of bipolar affective disorder using logistic models.

Data on bipolar affective disorder in 187 pedigrees from the Collaborative Depression Study were analyzed using logistic models that have been extended to incorporate age of onset information. Logistic regression analysis and segregation analysis revealed evidence for complex familial effects on this disorder.

Age Factors↗

Anthropometric variation and the genetic structure of the Jirels of Nepal.

Anthropometric measurements (head length, head breadth, bizygomatic diameter, minimum frontal diameter, head circumference, and stature) for 526 adult Jirels are utilized to establish the pattern of phenotypic relationships between seven villages in eastern Nepal. An analytical framework is provided that justifies the interpretation of biological distances as minimum genetic distances. Using this approach, estimates of the minimum pairwise genetic distances between villages and the minimum FST for the population are derived from the purely phenotypic data. The FST obtained in this way is consistent with results obtained from other data available for this population, confirming the utility of phenetic analysis of quantitative traits for elucidating genetic structure.

Anthropometry↗

ELA and fertility in American Standardbred horses.

We have analysed the effects of ELA alleles and sire-dam ELA incompatibility on two measures of fertility, gestation length and foaling rate, in American Standardbred horses. Using multivariate statistical methods, we corrected for the effects of confounding factors such as dam and sire age, parity, inbreeding, and sire-dam kinship. These analyses revealed substantial differences between Standardbred trotters and pacers in the effects of several confounding factors. There appear to be no ELA effects on gestation length in either trotters or pacers. However our results suggest that there may be ELA effects on foaling rate associated with specific dam alleles, with sire-dam incompatibility, and possibly with specific sire alleles, and that these effects differ between trotters and pacers.

Age Factors↗

Pedigree analysis of HDL cholesterol concentration in baboons on two diets.

Using complex segregation analysis, we examined the effects of genetic factors and diet on serum concentrations of high-density-lipoprotein cholesterol (HDL-C) in baboons. In analyses of 710 baboons in 23 sire families, we found evidence for a major gene as well as a polygenic contribution to HDL-C concentration in baboons fed a basal (chow) diet and also in the same animals after challenge with a high-cholesterol, saturated-fat diet. There was evidence for a polygenic contribution to the change in HDL-C concentration in response to the dietary challenge, but there was no evidence for a major gene effect.

Animals↗

The relationship of soluble ICAM-1, VCAM-1, P-selectin and E-selectin to cardiovascular disease risk factors in healthy men and women.

BACKGROUND: Clinical studies have shown that elevated serum concentrations of cell adhesion molecules such as inter-cellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin (ESEL) and P-selectin (PSEL) may be independent risk factors for atherosclerosis and cardiovascular disease (CVD). Less is known of the relationship of these inflammatory markers with established CVD risk factors in healthy individuals, particularly women. OBJECTIVE: The aim of this study was to examine cross-sectional relationships between the concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1, sPSEL and sESEL) and smoking behaviour, body composition, blood pressure, serum lipids and physical activity in a large sample of healthy men and women, with special emphasis on interactions between smoking and other CVD risk factors. SUBJECTS: The analysis included 592 healthy white adults aged 18-82 years. RESULTS: There were no sex differences in the concentrations of sICAM-1, sVCAM-1 and sPSEL, but men had higher sESEL levels than women (p < 0.0001). Male and female smokers had higher sICAM-1 and sESEL levels than non-smokers and soluble cell adhesion molecules (CAMs) were correlated with the pack-years of cigarette smoking (r = 0.3-0.4, p < 0.0001, significant in women only). Significant independent associations were found between soluble CAMs and smoking, waist-hip ratio (WHR), blood pressure, high density lipoprotein cholesterol and total cholesterol. Furthermore, significant interaction effects were found in women, such that the relationship between CAMs and lipid concentrations and WHR were stronger in smokers than non-smokers. In conclusion, the concentration of soluble CAMs, particularly sICAM-1 and sESEL, reflect the level of established CVD risk factors in apparently healthy men and women, adding to the evidence that these factors contribute to CVD through their inflammatory effects on the vascular endothelium.

Adult↗

Quantitative genetics of dehydroepiandrosterone sulfate and its relation to possible cardiovascular disease risk factors in Mexican Americans.

Dehydroepiandrosterone sulfate (DHEAS) is an adrenal steroid which has been inversely associated with development of atherosclerosis. We estimated heritability of serum DHEAS levels in 564 related Mexican Americans. We found a significant heritability for DHEAS (h2 = 0.39, p < 0.001). Measures of alcohol consumption, reproductive status, body composition, and HDL3 levels showed significant relationships with serum DHEAS levels. Sex and age were significantly associated with the mean, but not the genetic variance, of DHEAS levels. The results of this study demonstrate a significant genetic influence on steroid concentration and help to quantify the factors contributing to cardiovascular disease risk in Mexican Americans.

Adolescent↗

Genetic epidemiology of non-insulin-dependent diabetes mellitus (NIDDM) in north India: distribution of Gm and Km allotypes in 'Punjabis'.

Non-insulin dependent diabetes mellitus (NIDDM) is becoming endemic to modernizing and urbanizing populations all over the globe. The data on Gm and Km allotypes in the 'Punjabis' (n = 165) from north India show an interesting association with NIDDM. Differences between diabetic and control samples for the Km allele frequency distribution approach significance (p = 0.0897). The observed phenotypic diversity in the Gm system in diabetics indicates genetic heterogeneity in the disease group. A significant decrease (or absence) of phenotype Gm1,3,17; ;5,21 (p = 0.0119), and presence of phenotype Gm1,2,3,17; ;5,21 (p = 0.0158) in diabetics may constitute a risk factor for this disorder in 'Punjabis'.

Adult↗