Segregation analysis of HDL cholesterol in the NHLBI Family Heart Study and in Utah pedigrees.

We investigated the genetic determination of high-density-lipoprotein cholesterol (HDL-C) levels in the NHLBI Family Heart Study by segregation analysis. Included was a total of 3755 subjects from 560 randomly selected nuclear families and 522 families selected due to a high family risk of coronary heart disease (CHD). In the whole dataset, there was no evidence for an allele at a major gene locus responsible for HDL-C levels lower than the population mean or even for significant bimodality for low levels of HDL-C.

Genomewide linkage scan of resting blood pressure: HERITAGE Family Study. Health, Risk Factors, Exercise Training, and Genetics.

The purpose of this study was to search for genomic regions influencing resting systolic (SBP) and diastolic (DBP) blood pressure (BP) in sedentary families (baseline), and for resting BP responses (changes) resulting from a 20-week exercise training intervention (post-training-baseline) in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. A genome-wide scan was conducted on 317 black individuals from 114 families and 519 white individuals from 99 families using a multipoint variance-components linkage model and a panel of 509 markers. Promising results were primarily, but not exclusively, found in the black families.

Familial aggregation of blood lipid response to exercise training in the health, risk factors, exercise training, and genetics (HERITAGE) Family Study.

Background: Fasting levels of plasma lipids and lipoproteins are reported to improve with regular exercise training. However, little is known on whether the training responses are influenced by heritable factors.

Methods And Results: The lipid profile was assessed in 115 black (224 individuals) and 99 white families (469 individuals), who participated in the HERITAGE Family Study, while in a sedentary state (baseline visit) and after exercise training for 20 weeks (post visit).

Influence of apolipoprotein E, smoking, and alcohol intake on carotid atherosclerosis: National Heart, Lung, and Blood Institute Family Heart Study.

Background And Purpose: Apolipoprotein E (apoE) isoforms and lifestyle factors play an important role in the development of coronary heart disease. The association of apoE and carotid atherosclerosis remains controversial.

Methods: We investigated the relation of apoE, cigarette smoking, alcohol drinking, and their interaction with carotid atherosclerosis on 544 individuals free of coronary heart disease in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study.

Searching for the mountains of the moon: genome scans for atherosclerosis.

Several research groups have begun mounting large, ambitious family studies to map genes for atherosclerosis, heart disease, and their major risk factors using whole genome linkage and/or disequilibrium scans. Some of the problems, pitfalls, and challenges of this exciting effort are examined and illustrated with lessons from an earlier mapping problem.

Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction; airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC). To identify genetic determinants of quantitative spirometric phenotypes, an autosomal 10-cM genomewide scan of short tandem repeat (STR) polymorphic markers was performed in 72 pedigrees (585 individuals) ascertained through probands with severe early-onset COPD.

Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: airflow obstruction and chronic bronchitis phenotypes.

Familial aggregation of chronic obstructive pulmonary disease (COPD) has been demonstrated, but linkage analysis of COPD-related phenotypes has not been reported previously. An autosomal 10 cM genome-wide scan of short tandem repeat (STR) polymorphic markers was analyzed for linkage to COPD-related phenotypes in 585 members of 72 pedigrees ascertained through severe, early-onset COPD probands without severe alpha1-antitrypsin deficiency. Multipoint non-parametric linkage analysis (using the ALLEGRO program) was performed for qualitative phenotypes including moderate airflow obstruction [forced expiratory volume at one second (FEV(1)) < 60% predicted, FEV(1)/FVC < 90% predicted], mild airflow obstruction (FEV(1) < 80% predicted, FEV(1)/FVC < 90% predicted) and chronic bronchitis.

Quantitative-trait loci influencing body-mass index reside on chromosomes 7 and 13: the National Heart, Lung, and Blood Institute Family Heart Study.

Obesity is a risk factor for many chronic diseases, including glucose intolerance, lipid disorders, hypertension, and coronary heart disease. Even though the body-mass index (BMI) is a heterogeneous phenotype reflecting the amount of fat, lean mass, and body build, several studies have provided evidence of one or two major loci contributing to the variation in this complex trait. We sought to identify loci with potential influence on BMI in the data obtained from National Heart, Lung, and Blood Institute Family Heart Study.

Familial resemblance in fatness and fat distribution.

The purpose of the study was to estimate the degree of familial resemblance in anthropometric indicators of fatness and fat distribution. The sample consisted of 327 Caucasian participants from 102 nuclear families. Indicators of fatness included the body mass index (BMI), the sum of six skinfolds (SF6: triceps + biceps + medial calf + subscapular + suprailiac + abdominal), and waist circumference (WAIST), while indicators of fat distribution included WAIST adjusted for BMI (WAIST(ADJ)), the trunk-to-extremity skinfold ratio, adjusted for SF6 (TER(ADJ)), and the first principal component of skinfolds, adjusted for the mean skinfold of the individual (PC1).

Heterogeneity among populations for familial aggregation of blood pressure.

A simple model of familial aggregation was applied to age-sex corrected systolic (SBP) and diastolic (DBP) blood pressure data from two separate studies: The Québec Family Study and the Tecumseh Community Health Study. Examination of the familial correlations suggested heterogeneity across studies in all DBP correlations, but for SBP only spouse correlations were higher in Québec. Fitting the path model to the data revealed that the only source of heterogeneity for SBP was in spouse resemblance (u), which was significant in Québec but could be dropped from the model in Tecumseh.