Biomedical subjects

D C Rao

Publications and source records attributed to D C Rao.

At least 91 records · Page 5Linked to original sources

PubMed2003

Influence of fat-free mass on detection of appropriateness of left ventricular mass: the HyperGEN Study.

OBJECTIVES: To evaluate the differences between using height(2.7) or fat-free mass for assessment of the appropriateness of left ventricular mass (LVM) in relation to hemodynamic load, and to evaluate the performance of Doppler as compared with M-mode-derived stroke volume for computation of predicted values of LVM. DESIGN: Cross-sectional. SETTING: Population-based. PARTICIPANTS: We studied 2299 participants from the Hypertension Genetic Epidemiology Network Study (prevalent cardiovascular disease in 342). OUTCOME MEASURES: Individual predicted values of LVM were generated by equations using sex, stroke work (systolic blood pressure x stroke volume by either Doppler or M-mode) and either height(2.7) or fat-free mass, as measures of body build, in 228 normotensive, non-obese, non-diabetic participants. Observed LVM was divided by the predicted value and evaluated as 'excess of LVM'. RESULTS: Among 1957 participants without prevalent cardiovascular disease, obese individuals (n = 1008) were slightly younger than non-obese individuals, whereas diabetic participants (n = 294) were slightly older. Excess of LVM was positively related to body mass index (BMI), independently of echocardiographic method and measure of body build, especially when height(2.7) and m-mode stroke work were used, and was greatest in the presence of concentric left ventricular hypertrophy (P < 0.0001). Excess LVM by height(2.7) was progressively greater than that by fat-free mass, as BMI increased (P < 0.0001). In analyses of covariance of association of prevalent cardiovascular disease with age, sex, race, BMI, and excess of LVM (by each method), methods using height(2.7) were more associated with prevalent cardiovascular disease than were methods using fat-free mass (P < 0.02). CONCLUSIONS: Deviation of LVM from values that compensate hemodynamic load can be similarly identified using different measures of body build and methods to generate stroke work. However, the use of height(2.7) to compute LVM as a percentage of that predicted appears to identify deviations from compensatory values that are independently related to prevalent cardiovascular disease more effectively than does the use of fat-free mass.

Adult↗

PubMed2003

Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study.

The metabolic syndrome involves multiple and interactive effects of genes and environmental factors. To identify chromosomal regions encoding genes possibly predisposing to the metabolic syndrome, we performed a genome-wide scan with 456 white and 217 black participants from 204 nuclear families of the HERITAGE Family Study, using regression-based, single- and multipoint linkage analyses on 509 markers. A principal component analysis was performed on 7 metabolic syndrome-related phenotypes. Two principal components, PC1 and PC2 (55% of the variance), were used as metabolic syndrome phenotypes. ANOVA was used to quantify the familial aggregation of PC1 and PC2. Family membership contributed significantly (P < 0.0023) to the variance in PC1 (r(2) = 0.38 in whites; r(2) = 0.55 in blacks) and PC2 (r(2) = 0.51; r(2) = 0.48). In whites, promising evidence for linkage (P < 0.0023) was found for PC1 (2 markers on 10p11.2) and PC2 (a marker on 19q13.4). Suggestive evidence of linkage (0.01 > P > 0.0023) appeared for PC1 (1q41 and 9p13.1) and PC2 (2p22.3). In blacks, promising linkage was found for PC2 on 1p34.1, and suggestive linkage was found on 7q31.3 and 9q21.1. The genome-wide scan revealed evidence for quantitative trait loci on chromosomal regions that have been previously linked with individual cardiovascular disease and type 2 diabetes risk factors. Some of these chromosomal regions harbor promising potential candidate genes.

Adolescent↗

PubMed2003

Genome-wide linkage scan for physical activity levels in the Quebec Family study.

PURPOSE AND METHODS: It is commonly recognized that there is familial aggregation for physical activity level. However, the genes and sequence variants responsible for the familial clustering have not been investigated. We performed a genome-wide linkage scan based on 432 markers typed in 767 subjects from 207 families of the Quebec Family study with the aim of identifying loci affecting physical activity levels. Four physical activity level phenotypes were used. RESULTS: Promising evidence of linkage (P < 0.0023) was found for physical inactivity on chromosome 2p22-p16. Suggestive linkages (0.0023<P < 0.01) were found for inactivity (7p11.2, 20q13.1), total physical activity (13q22-q31), moderate to strenuous physical activity (4q28.2, 7p11.2, 9q31.1, 13q22-q31), and time spent in physical activity (11p15 and 15q13.3). CONCLUSION: This study identified several chromosomal regions harboring genes that may contribute to the propensity to be physically active or sedentary.

Adult↗

PubMed2003

Familial resemblance for muscle phenotypes in the HERITAGE Family Study.

INTRODUCTION/PURPOSE: We hypothesized that skeletal muscle histological and biochemical phenotypes aggregate within families. METHODS: Nineteen families (78 Caucasians) from the HERITAGE Family Study participated in the study. Proportions and areas of Type I, IIA, and IIX muscle fibers, capillary density, and maximal enzyme activities were determined in biopsy samples from the vastus lateralis obtained in the sedentary state and after a 20-wk endurance-training program. RESULTS: In the sedentary state, there was evidence for familial resemblance for Type I fiber area (P = 0.007), number of capillaries around Type I and Type IIA fibers (P = 0.04), and Type I and IIA fiber areas per capillary (P = 0.01 and P = 0.04, respectively). Significant familial aggregation (0.05>P > 0.0001) was observed for maximal activities of enzymes of the energy production pathways. With regard to the training response, significant familial aggregation (0.05 > P < 0.0001) was observed for maximal activities of enzymes of the energy production pathways. CONCLUSION: These data provide evidence of familial aggregation for enzyme activities of the main energy metabolism pathways of the skeletal muscle in the sedentary state and in response to regular exercise.

Adaptation, Physiological↗

PubMed2003

Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study.

PURPOSE: To determine the efficacy of exercise training in treating the metabolic syndrome. METHODS: The sample included 621 black and white participants from the HERITAGE Family Study, identified as sedentary and apparently healthy (no chronic disease or injury). The metabolic syndrome was defined as having three or more risk factors according to the guidelines of the National Cholesterol Education Program, including elevated waist circumference, blood pressure, triglycerides, blood glucose, and low HDL cholesterol. The presence of the metabolic syndrome and component risk factors were determined before and after 20 wk of supervised aerobic exercise training. RESULTS: The prevalence of the metabolic syndrome was 16.9% in this sample (105/621) of apparently healthy participants. Of the 105 participants with the metabolic syndrome at baseline, 30.5% (32 participants) were no longer classified as having the metabolic syndrome after the exercise training. Among the 32 participants who improved their metabolic profile, 43% decreased triglycerides, 16% improved HDL cholesterol, 38% decreased blood pressure, 9% improved fasting plasma glucose, and 28% decreased their waist circumference. There were no sex or race differences in the efficacy of exercise in treating the metabolic syndrome: 32.7% of men, 28.0% of women, 29.7% of black, and 30.9% of white participants with the metabolic syndrome were no longer classified as having the syndrome after training. CONCLUSION: Aerobic exercise training in patients with the metabolic syndrome can be useful as a treatment strategy and provides support for a role for physical activity in the prevention of chronic disease.

Adult↗

PubMed2003

Heart rate versus %VO2max: age, sex, race, initial fitness, and training response--HERITAGE.

PURPOSE: In the HERITAGE Family Study, heart rate (HR) associated with various percentages of maximal oxygen intake (VO2max) was used to prescribe exercise intensity. When fitness improved, HR at the same power output (PO) decreased, and PO was increased to produce the prescribed HR. Although we assumed that subjects were again working at the same %VO2max, there were no studies with a large heterogeneous population to determine whether this was correct. METHODS: Therefore, 653 subjects with complete data were classified by age, sex, race, initial VO2max, and VO2max response after 20 wk of training. RESULTS: All groups had a significant increase in VO2max and a significant decrease in HR at the same absolute PO after training but no difference in HR at the same relative intensity. CONCLUSIONS: Training does not affect HR at a given %VO2max in a heterogeneous population of men and women, blacks and whites aged 17-65 yr with different initial VO2max values and different responses to training.

Adolescent↗

PubMed2003

A quantitative trait locus on 7q31 for the changes in plasma insulin in response to exercise training: the HERITAGE Family Study.

Several genome-wide linkage scans have been carried out to identify quantitative trait loci for type 2 diabetes and related metabolic phenotypes. However, no previous linkage scans have focused on the response to exercise training of relevant metabolic traits. We performed a genome-wide linkage scan for baseline fasting glucose, insulin, and C-peptide and their responses to a 20-week exercise training program in nondiabetic white and black men and women from the HERITAGE Family Study. In SIBPAL linkage analyses, the maximum number of sibpairs available was 344 and 93 for baseline phenotypes and 300 and 72 for exercise training response phenotypes in whites and blacks, respectively. A total of 509 markers with an average spacing of 6.0 Mb were used. The strongest linkage was found for the changes in fasting insulin in response to exercise training with a marker in the leptin gene on 7q31 (empirical multipoint P = 0.0004) in whites. In blacks, the strongest linkage was observed for baseline fasting glucose on 12q13-q14 (empirical multipoint P = 0.0006). These regions harbor several potential candidate genes. The present findings may be important in identifying individuals at increased risk of developing type 2 diabetes and who are most likely to benefit from a physically active lifestyle.

Black People↗

PubMed2002

Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study.

A genome-wide linkage scan was performed for genes affecting submaximal exercise cardiac output (Q) and stroke volume (SV) in the sedentary state and their responses to a standardized 20-wk endurance training program. A total of 509 polymorphic markers were used, and 328 pairs of siblings from 99 white nuclear families and 102 sibling pairs from 105 black family units were available. Q and SV were measured in relative steady state during exercise at 50 W (Q50 and SV50, respectively). Baseline phenotypes were adjusted for age, sex, and body surface area (BSA), and the training responses (post-training - baseline, Delta) were adjusted for age, sex, baseline BSA, and baseline value of the phenotype. Three analytical strategies were used: a multipoint variance components linkage analysis using all the family data, and regression-based single- and multipoint linkage analyses using pairs of siblings. In whites, baseline SV50 and DeltaSV50 showed promising linkages (P < 0.0023) with markers on chromosomes 14q31.1 and 10p11.2, respectively. Suggestive evidence of linkage (0.01 > P > 0.0023) for DeltaSV50 and Delta Q50 was detected on chromosome 2q31.1 and for baseline SV50 and Q50 on chromosome 9q32-q33. In blacks, markers on 18q11.2 showed promising linkages with baseline Q50. Suggestive evidence of linkage was found in three regions for baseline SV50 (1p21.3, 3q13.3, 12q13.2) and one for baseline SV50 and Q50 (10p14). All these chromosomal regions include several potential candidate genes and therefore warrant further studies in the HERITAGE cohort and other studies.

Adult↗

PubMed2002

Gender difference in diastolic function in hypertension (the HyperGEN study).

Although several studies indicate that there are gender differences in left ventricular (LV) systolic function, it remains unclear whether similar differences exist with regard to diastolic function. Accordingly, Doppler echocardiograms were analyzed in 515 male and 839 female, mostly treated (95%) hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study with no evidence of abnormal wall motion or significant valvular heart disease. There was no difference in age between genders, but after adjusting for age and race, men had lower body mass indexes (29.8 +/- 5.2 vs 32.3 +/- 7.6 kg/m(2)) and heart rates (67 +/- 12 vs 69 +/- 11 beats/min) and higher systolic and diastolic blood pressures (BP) than women (134 +/- 20 vs 130 +/- 21 and 80 +/- 11 vs 72 +/- 11 mm Hg, all p <0.001). LV mass/height(2.7) was slightly greater in women than in men (43 +/- 10 vs 42 +/- 9 g/m(2.7), p <0.05). After adjusting for age, race, systolic BP, body mass index, heart rate, and LV hypertrophy, both mitral E-wave (70 +/- 18 vs 77 +/- 19) and A-wave (74 +/- 15 vs 79 +/- 17, both p <0.001) velocities were lower in men than in women, but the mitral E/A ratio and atrial filling fraction were nearly identical in both genders. Deceleration time (221 +/- 55 vs 214 +/- 46 cm/s, p = 0.018) and isovolumic relaxation time (IVRT) were longer in men than in women (85 +/- 18 vs 81 +/- 17 cm/s, p <0.001). Prolonged IVRT was present in more men than women (14% vs 7%, p <0.05). In analyses of covariance, adjusting for age, race, systolic BP, body mass index, heart rate, and medications, male gender remained related to prolonged deceleration time and IVRT. Thus, in this population-based sample of hypertensive adults, men had evidence of slower early diastolic LV filling than women. This gender difference in diastolic function may provide insight into gender differences in congestive heart failure and other specific cardiovascular diseases.

Age Distribution↗

PubMed2002

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). Variables included total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I, and HDL-C subfractions 2 (HDL2-C) and 3 (HDL3-C). Familial correlations for the training responses (Delta=post-baseline) were significant for most variables, and the percent variance accounted for by familial factors (ie, maximal heritabilities) ranged from 25% to 38%. Exceptions were for higher heritabilities near 60% for DeltaApoB in blacks and DeltaHDL2-C in whites and a lower estimate of zero for DeltaLDL-C in blacks. CONCLUSIONS: Heritable factors in part determine lipid profile responses to regular exercise. Maximal heritabilities were similar across ethnic groups and variables, except for DeltaLDL-C, DeltaApoB, and DeltaHDL2-C. Molecular studies to identify the markers and genes associated with these influences are currently underway.

Adolescent↗

PubMed2002

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. Multipoint variance-component linkage analysis (using SOLAR) was performed for quantitative phenotypes, including FEV(1), FVC, and FEV(1)/FVC. In the initial genomewide scan, significant evidence for linkage to FEV(1)/FVC was demonstrated on chromosome 2q (LOD score 4.12 at 222 cM). Suggestive evidence was found for linkage to FEV(1)/FVC on chromosomes 1 (LOD score 1.92 at 120 cM) and 17 (LOD score 2.03 at 67 cM) and to FVC on chromosome 1 (LOD score 2.05 at 13 cM). The highest LOD score for FEV(1) in the initial genomewide scan was 1.53, on chromosome 12, at 36 cM. After inclusion of 12 additional STR markers on chromosome 12p, which had been previously genotyped in this population, suggestive evidence for linkage of FEV(1) (LOD score 2.43 at 37 cM) to this region was demonstrated. These observations provide both significant evidence for an early-onset COPD-susceptibility locus on chromosome 2 and suggestive evidence for linkage of spirometry-related phenotypes to several other genomic regions. The significant linkage of FEV(1)/FVC to chromosome 2q could reflect one or more genes influencing the development of airflow obstruction or dysanapsis.

Adult↗

PubMed2002

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. The strongest evidence for linkage in all subjects was observed at chromosomes 12 (LOD = 1.70) and 19 (LOD = 1.54) for moderate airflow obstruction, chromosomes 8 (LOD = 1.36) and 19 (LOD = 1.09) for mild airflow obstruction and chromosomes 19 (LOD = 1.21) and 22 (LOD = 1.37) for chronic bronchitis. Restricting analysis to cigarette smokers only provided increased evidence for linkage of mild airflow obstruction and chronic bronchitis to several genomic regions; for mild airflow obstruction in smokers only, the maximum LOD was 1.64 at chromosome 19, whereas for chronic bronchitis in smokers only, the maximum LOD was 2.08 at chromosome 22. On chromosome 12p, 12 additional STR markers were genotyped, which provided additional support for an airflow obstruction locus in that region with a non-parametric multipoint approach for moderate airflow obstruction (LOD = 2.13) and mild airflow obstruction (LOD = 1.43). Using a dominant model with the STR markers on 12p, two point parametric linkage analysis of all subjects demonstrated a maximum LOD score of 2.09 for moderate airflow obstruction and 2.61 for mild airflow obstruction. In smokers only, the maximum two point LOD score for mild airflow obstruction was 3.14. These observations provide suggestive evidence that there is a locus on chromosome 12p which contributes to susceptibility to early-onset COPD.

Adult↗

PubMed2002

G protein beta 3 polymorphism and hemodynamic and body composition phenotypes in the HERITAGE Family Study.

A C825T polymorphism of the G protein beta3 (GNB3) gene has been reported to be associated with hypertension and obesity. We analyzed the associations between the GNB3 C825T polymorphism and hemodynamic and body composition phenotypes in the sedentary state and their responses to endurance training in mainly normotensive white (n = 473) and black (n = 255) men and women. Blood pressure (BP) and heart rate (HR) were measured at rest and during submaximal exercise at constant power output (50 W), and stroke volume and cardiac output were obtained during exercise. Body composition was assessed with underwater weighing. Baseline systolic BP (SBP) at 50 W was slightly higher in the white CC homozygotes (P = 0.036), whereas in blacks the CC genotype was associated with a lower resting HR (P = 0.012). In blacks, the CC homozygotes showed a greater training-induced reduction in HR at 50 W (P = 0.013) and a similar trend was observed also in whites (P = 0.053). Black women carrying the CC genotype showed significantly greater reductions in resting SBP and diastolic BP (DBP) than the TT homozygotes, whereas in black men the changes in resting BP were similar across the genotypes (P < 0.05 for sex-by-GNB3 interactions). The GNB3 genotype was not associated with baseline body composition in blacks or whites. In blacks, the TT genotype was associated with a greater training-induced decrease in fat mass (P = 0.012) and percent body fat (P = 0.006). These data suggest that DNA sequence variation in the GNB3 locus is not a major modifier of endurance training-induced changes in hemodynamic and body composition phenotypes in healthy but previously sedentary subjects. The GNB3 genotype may play a minor role in HR and body fatness regulation in blacks and in responsiveness of resting BP to endurance training in black women.

Adult↗

PubMed2002

Role of gene expression microarray analysis in finding complex disease genes.

The promise of gene expression studies using microarray technology has inspired much new hope for finding complex diseases genes. It has become clear that complex diseases result from collective actions of many genetic and nongenetic factors. Therefore, genetic dissection of complex diseases should be carried out in a global context. The technology of gene expression microarray analysis (GEMA) can provide such global information on transcription activities of essentially all genes simultaneously. It is hoped that this promising technology can be applied to samples drawn from large-scale, well-defined genetic epidemiological studies and help us untangle the web of pathways leading to complex diseases. However, extremely noisy GEMA data pose serious challenges in terms of the statistical methodologies needed. Extensive work is needed in order to respond to the challenges before one can fully utilize the potential power provided by GEMA. We begin in this paper by identifying several statistical problems related to the application of GEMA to genetic epidemiological analysis, and consider study designs that might benefit from this promising new technology. While it is still too early to tell how much of the enormous potential of GEMA will be realized ultimately, its success will probably depend most critically on the ability of statistical genetics to rise to the challenge of mining information from a sea of noise.

Gene Expression↗

PubMed2002

Role of ghrelin polymorphisms in obesity based on three different studies.

OBJECTIVE: Associations between preproghrelin DNA variants and obesity-related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study. RESEARCH METHODS AND PROCEDURES: Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction. RESULTS: Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p = 0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the lowest FM (p < 0.001). Met72 carrier status (Met72+) was associated with lower FM (p = 0.026) and higher insulin-like growth factor-1 levels (p = 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p < 0.05) in SOS subjects whose BMI was < or =25 kg/m(2) than in those with BMI >25 kg/m(2) (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence of hypertension than noncarriers (23.9%). DISCUSSION: Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.

Abdomen↗

PubMed2002

Pleiotropic relationships between cortisol levels and adiposity: The HERITAGE Family Study.

OBJECTIVE: To investigate familial basis for the relationship between cortisol adiposity at baseline and their training responses. RESEARCH METHODS AND PROCEDURES: Bivariate correlation and segregation analyses were employed between cortisol and several adiposity measures [body mass index, fat mass (FM), fat-free mass, percentage of body fat (% BF), abdominal visceral fat (AVF), abdominal subcutaneous fat (ASF), and abdominal total fat (ATF)] from 99 white families and 105 black families. RESULTS: In both races, significant inverse phenotypic correlations were generally observed between cortisol and adiposity measures at baseline but not for training responses. Significant cross-trait familial correlations were found for cortisol with abdominal fat (ASF, AVF, ATF) and overall body adiposity (FM, % BF) measures at baseline, which accounted for 14% to 20% of the phenotypic variance in whites. The cross-trait correlations were not significant for baseline phenotypes in blacks, perhaps because of the small sample size. A bivariate segregation analysis showed evidence of polygenic pleiotropy for cortisol with both abdominal fat and overall adiposity measures that accounted for 14% to 17% of the phenotypic covariance, but major gene pleiotropy was not suggested in whites. However, when ASF, AVF, and ATF were additionally adjusted for FM, no familial cross-trait correlations or polygenic pleiotropy between cortisol and the abdominal fat measures remained. DISCUSSION: Evidence was found for polygenic pleiotropy but not for pleiotropic major gene effects between cortisol and overall adiposity in whites. However, the covariation of cortisol with abdominal fat phenotypes is dependent on concomitant polygenic factors for total-body fat.

Abdomen↗

PubMed2002

Familial resemblance for plasma leptin: sample homogeneity across adiposity and ethnic groups.

OBJECTIVE: Previous studies show a wide range in the percentage of variance in leptin levels attributable to genetic factors. These studies differ markedly with respect to ethnicity, study design, and statistical methodology. Therefore, the purpose of this study was to investigate heterogeneity hypotheses across ethnic groups and by adiposity level, using the same statistical methods. RESEARCH METHODS AND PROCEDURES: Samples included black vs. white (HERITAGE Family Study) and random vs. obese (Québec Family Study) individuals from 432 families (1432 individuals). Heritability for leptin, alternatively adjusted for age and sex and then for age, sex, and adiposity was estimated with the use of familial correlations. Heterogeneity in the magnitude of the familial resemblance between samples and the effect of adjusting for adiposity was explored. RESULTS: Heritability did not vary across samples stratified by adiposity level or ethnic group or across adjustment schemes. Maximal heritability, the percentage of additive phenotypic variability due to all familial sources, was 32%. DISCUSSION: Whereas leptin and adiposity were highly correlated within individuals, removing the effects of adiposity did not significantly alter the magnitude of the familial component for leptin. Moreover, this effect did not vary as a function of ethnicity (black vs. white) or adiposity level. Thus, no evidence for heterogeneity was detected. However, a comparison among previous studies raises questions concerning possible genetic heterogeneity in other ethnic groups in which complex interactions among leptin, adiposity, and diabetes status may be important.

Adipose Tissue↗

PubMed2002

Familial resemblance of 7-year changes in body mass and adiposity.

OBJECTIVE: To investigate the familial resemblance of 7-year changes in body mass and adiposity among Canadian families. RESEARCH METHODS AND PROCEDURES: The sample consisted of 655 women and 660 men from 521 families who participated in the Canada Fitness Survey in 1981 and the follow-up Campbell's Survey in 1988. Indicators of baseline and 7-year changes in body mass and adiposity included body mass (kilograms), body mass index (BMI; kilograms per square meter), sum of five skinfolds (SF5; millimeters), and waist circumference (WC; millimeters). The data were adjusted for the effects of age and sex, and the change scores were adjusted for baseline levels. A familial correlation model was used to determine the heritability of each phenotype using maximum likelihood techniques. RESULTS: Significant familial resemblance was observed at baseline and for 7-year changes in all phenotypes. At baseline, moderate heritabilities were observed [body mass: heritability coefficient (h(2)) = 56%; BMI, h(2) = 39%; SF5, h(2) = 41%; and WC, h(2) = 39%], whereas values were attenuated for each change score except for WC (Deltabody mass, h(2) = 23%; DeltaBMI, h(2) = 14%; DeltaSF5, h(2) = 12%; and DeltaWC, h(2) = 45%). DISCUSSION: Changes in body mass and adiposity significantly aggregate within families over 7 years. However, baseline values are characterized by higher heritability levels except WC. The significant heritabilities observed for change scores suggest that lifestyle, transient environmental factors, and possibly age-related gene effects are important determinants of changes in body mass and adiposity.

Adipose Tissue↗