Reproducibility of anthropometric and body composition measurements: the HERITAGE Family Study.

Objective: To determine the reproducibility of anthropometric and body composition measures using the HERITAGE Family Study protocol.

Design: Anthropometric and body composition measures were obtained on three separate days within a 3-wk period at each of the four HERITAGE Clinical Centers.

Subjects: Sixty men and women representative of the HERITAGE subject population, 15 from each of four Clinical Centers.

Principal components analysis of morphological measures in the Québec family study: Familial correlations.

Principal components analysis was carried out on 13 morphological dimensions collected in the first phase of the Québec Family Study (weight, height, fat mass (FM), fat-free mass (FFM), body surface area, six skinfolds, arm and calf girths). The first four principal components (PCs) account for 85.9% of the total phenotypic variance in the anthropometric dimensions.

Race differences in reproducibilities: The HERITAGE family study.

The HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study is a multicenter clinical trial conducted by five institutions in the United States and Canada. The overall objective of the study is to investigate the role of the genotype in cardiovascular, metabolic, and hormonal responses to aerobic exercise training and the contribution of regular exercise to changes in cardiovascular disease and diabetes risk factors in white and black families. Since the accuracy of the assessment of the response to training depends on how repeatable or reproducible the measurements are, it is important to assess potential racial differences in reproducibilities, which may have implications for pooling data across races.

The role of smoothing techniques in the interpretation of results from genomic scans using sib-pair data.

We compare the results of genomic scans conducted with the Haseman-Elston sib-pair method using either (1) the average marker information from several adjacent loci or (2) each marker individually. Under smoothing, the squared sib-pair trait difference is regressed on the average number of alleles shared identical by descent averaged at several adjacent loci. This results in a significant decrease in the number of false-positives when compared to the individual marker approach.

Genome screening using extremely discordant and extremely concordant sib pairs.

We applied extreme sib-pair methods in two ways to the GAW10 Problem 2A data sets to detect susceptible quantitative trait loci using extremely discordant sib pairs only, and combining them with the available extremely concordant sib pairs as suggested by the authors elsewhere. Ten successive original replicates were combined into one sampling pool so as to get the necessary number of extreme sib pairs. A total of 100 replicates were used to produce 10 such data sets for both initial detection and confirmations.

Trade-off between false positives and false negatives in the linkage analysis of complex traits.

This study examines the issue of false positives in genomic scans for detecting complex trait loci using subpair linkage methods and investigates the trade-off between the rate of false positives and the rate of false negatives. It highlights the tremendous cost in terms of power brought about by an excessive control of type I error and, at the same time, confirms that a larger number of false positives can occur otherwise in the course of a genomic scan. Finally, it compares the power and rate of false positives obtained in preplanned replicated studies conducted using a liberal significance level to those for single-step studies that use the same total sample size but stricter levels of significance.

Linkage analysis of complex traits using affected sibpairs: effects of single-locus approximations on estimates of the required sample size.

We investigated the power of the affected sibpair method for detecting a disease locus when the disease is inherited through two bi-allelic loci. The power was computed for all possible values of the gene frequencies and penetrances that lead to a given population prevalence and a given sibling relative risk. A method to generate rapidly all possible models that give a specific population prevalence and relative risk is provided.

Associations of candidate loci angiotensinogen and angiotensin-converting enzyme with severe hypertension: The NHLBI Family Heart Study.

Purpose: In studies conducted in several different populations, the M235T substitution in the angiotensinogen (AGT) locus has been associated with hypertension.

Methods: A case-control study was initiated in an attempt to replicate this finding. Persons with hypertension, age- and sex-matched normotensive controls, and randomly sampled individuals were probands from the Family Heart Study of the National Heart, Lung, and Blood Institute.

Associations between candidate loci angiotensin-converting enzyme and angiotensinogen with coronary heart disease and myocardial infarction: the NHLBI Family Heart Study.

Angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) are major components of the renin-angiotensin systems. An association between myocardial infarction (MI) and the ACE DD genotype of the insertion/deletion (ID) polymorphism in intron 16 of the ACE gene has been reported. However, other similarly designed studies have not found such an association.

Family history of coronary heart disease and hemostatic variables in middle-aged adults. Atherosclerosis Risk in Communities Investigators and Family Heart Study Research Group.

Individuals with a family history of coronary heart disease (CHD) may be predisposed to atherothrombosis. To investigate this hypothesis, a family CHD risk score was computed for approximately 13,000 men and women aged 45 to 64; hemostatic variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand factor, antithrombin III. protein C) were also measured in plasma.

Trade-off between sibship size and sampling scheme for detecting quantitative trait loci.

There is general consensus that linkage with a quantitative trait locus cannot be detected with a reasonable number of sibpairs unless that trait has a very high heritability or the pairs are highly selected. However, the latter may require the screening of a very large number of pairs before a relatively small number of highly informative pairs is attained. At the same time, it is known that, for the same number of typed individuals, larger sibships tend to provide more linkage information than do independent sibpairs.

The HERITAGE Family Study: quality assurance and quality control.

The HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study is the first multicenter family clinical trial of its kind. Conducted by a consortium of five universities in the United States and Canada, the study has as its primary goal to document the role of the genotype in the cardiovascular, metabolic, and hormonal responses to aerobic exercise training. A comprehensive protocol was implemented at four Clinical Centers (CC) for the generation of data on sedentary subjects.

Familial correlations in the Québec family study: cross-trait familial resemblance for body fat with plasma glucose and insulin.

This study represents one component in our investigation of the familial factors underlying the insulin resistance (or metabolic) syndrome involving obesity, hyperinsulinaemia, glucose intolerance, dyslipidaemia, and hypertension. Here we examine the cross-trait familial resemblance between four measures of body size (two assessing total fat [body mass index and sum of six skinfolds] and two assessing fat patterning [ratio of trunk skinfold sum to extremity skinfold sum, adjusted and unadjusted for total subcutaneous fat]) with fasting plasma levels of glucose, insulin, and the ratio of insulin to glucose (IGR) in non-diabetic families participating in phase 1 of the Québec Family Study. A bivariate familial correlation model assessed both intraindividual (e.

A major gene for resting metabolic rate unassociated with body composition: results from the Québec Family Study.

A major gene hypothesis for resting metabolic rate (RMR) was investigated using segregation analysis (POINTER) of data on families participating in Phase 2 of the Québec Family Study. Complete analyses were conducted on RMR adjusted for age, and also on RMR adjusted for age and other covariates, primarily fat mass (FM) and fat-free mass (FFM). Prior to adjustment for covariates, support for a major gene hypothesis was equivocal-i.

Endurance exercise training has a minimal effect on resting heart rate: the HERITAGE Study.

This study determined the effects of a 20-wk endurance training program (The HERITAGE Family Study) on resting heart rate (HRrest). HRrest was obtained on a sample of 26 men and 21 women during sleep; during resting metabolic rate and resting blood pressure measurement periods in the early morning following a 12-h fast and 24-h post-exercise; and at rest prior to a maximal bout of exercise. Following training, the subjects exhibited a 16.

NHLBI Family Heart Study: objectives and design.

The NHLBI Family Heart Study is a multicenter, population-based study of genetic and nongenetic determinants of coronary heart disease (CHD), atherosclerosis, and cardiovascular risk factors. In phase I, 2,000 randomly selected participants and 2,000 with family histories of CHD were identified among 14,592 middle-aged participants in epidemiologic studies. Medical histories from these individuals, their parents, and their siblings were used to calculate family risk scores that compared the number of reported and validated CHD events with the number expected based on the size, sex, and age of family members.

Familial clustering of abdominal visceral fat and total fat mass: the Québec Family Study.

The evidence for common familial factors underlying total fat mass (estimated from underwater weighing) and abdominal visceral fat (assessed from CT scan) was examined in families participating in phase 2 of the Québec Family Study (QFS) using a bivariate familial correlation model. Previous QFS investigations suggest that both genetic (major and polygenic) and familial environmental factors influence each phenotype, accounting for between 55% to 71% of the phenotypic variance in fat mass, and between 55% to 72% for abdominal visceral fat. The current study suggests that the bivariate familial effect ranges from 29% to 50%.

Major gene for abdominal visceral fat area in the Québec Family Study.

Objectives: The abdominal visceral fat depot is considered to be the most atherogenic, diabetogenic and hypertensiogenic fat depot of the human body. Although the amount of abdominal visceral fat is correlated with total body fat, there remain considerable inter-individual differences in visceral fat at any level of body fat content. No study has been reported to date on the contribution of genetic factors to the variability in abdominal visceral fat level.

Genetic pleiotropy for resting metabolic rate with fat-free mass and fat mass: the Québec Family Study.

Shared genetic and familial environmental causes for the associations among resting metabolic rate (RMR), fat-free mass (FFM), and fat mass (FM) were investigated in families participating in phase 2 of the Québec Family Study. A multivariate familial correlation model assessing the pattern of significant cross-trait correlations between family members (e.g.

Familial aggregation of abdominal visceral fat level: results from the Quebec family study.

The purpose of this study was to investigate the importance of familial aggregation in abdominal visceral fat (AVF) level as assessed by computed tomography (CT). Four measures of abdominal adipose tissue, obtained from an abdominal scan between the fourth and fifth Lumbar vertebrae (L4-L5) taken in 366 adult subjects from 100 French-Canadian nuclear families, were considered in this study. Total abdominal fat, AVF, subcutaneous abdominal fat, obtained by computing the difference between total and AVF tissue areas, and the visceral to total abdominal fat ratio were measured.

Familial aggregation of subcutaneous fat patterning: Principal components of skinfolds in the Québec family study.

Familial resemblance was examined for each of the principal components arising from an analysis of six skinfolds (triceps, biceps, subscapular, abdominal, suprailiac, and medial calf) measured in 1,237 participants of the Québec Family Study. Most of the phenotypic variance among the skinfolds (83%) was accounted for by the first two principal components. Examination of the skinfold loadings on each principal component, as well as intraindividual cross-trait correlations with other body composition and fat pattern measures (body mass index; total fat mass and fat-free mass estimated from body density obtained through underwater weighing; the sum of six skinfolds; and the ratio of trunk to extremity skinfolds) support the interpretation of the first component as a general measure of adiposity and the second component as a trunk-extremity contrast.

Combining extremely concordant sibpairs with extremely discordant sibpairs provides a cost effective way to linkage analysis of quantitative trait loci.

Extremely discordant (ED) sibpairs have been shown to be very powerful for linkage analysis of human quantitative traits [Risch and Zhang (1995) Science 268: 1584-1589]. In many cases, the extremely concordant (EC) sibpairs collected in the process of screening for ED sibpairs carry valuable information for linkage. Therefore, it seems justifiable to investigate the advantages of genotyping and to include them with the ED sibpairs for linkage analysis.

Random effects model for meta-analysis of multiple quantitative sibpair linkage studies.

The growing interest in detection of genetic effects for complex traits along with molecular revolution has stimulated many linkage studies. Multiple replication studies tend to produce different results. In such situations, rigorous meta-analysis methods can be useful for assessing the overall evidence for linkage.

Genetic epidemiology of the Mitsuda reaction in leprosy.

This study comprised 544 nuclear families with 2,925 individuals tested for the Mitsuda reaction, from the Campinas region in Brazil. Segregation analyses suggest the segregation of a major gene (chi 2(1) = 0.07 - 0.