Biomedical subjects

Stefan A Czerwinski

Publications and source records attributed to Stefan A Czerwinski.

12 recordsLinked to original sources

PubMed2006

Quantitative genetics of cortical bone mass in healthy 10-year-old children from the Fels Longitudinal Study.

The genetic influences on bone mass likely change throughout the life span, but most genetic studies of bone mass regulation have focused on adults. There is, however, a growing awareness of the importance of genes influencing the acquisition of bone mass during childhood on lifelong bone health. The present investigation examines genetic influences on childhood bone mass by estimating the residual heritabilities of different measures of second metacarpal bone mass in a sample of 600 10-year-old participants from 144 families in the Fels Longitudinal Study. Bivariate quantitative genetic analyses were conducted to estimate genetic correlations between cortical bone mass measures, and measures of bone growth and development. Using a maximum likelihood-based variance components method for pedigree data, we found a residual heritability estimate of 0.71 for second metacarpal cortical index. Residual heritability estimates for individual measures of cortical bone (e.g., lateral cortical thickness, medial cortical thickness) ranged from 0.47 to 0.58, at this pre-pubertal childhood age. Low genetic correlations were found between cortical bone measures and both bone length and skeletal age. However, after Bonferonni adjustment for multiple testing, rho(G) was not significantly different from 0 for any of these pairs of traits. Results of this investigation provide evidence of significant genetic control over bone mass largely independent of maturation while bones are actively growing and before rapid accrual of bone that typically occurs during puberty.

Bone Density↗

PubMed2006

Do changes in body mass index percentile reflect changes in body composition in children? Data from the Fels Longitudinal Study.

OBJECTIVE: Our aim was to examine the degree to which changes in BMI percentile reflect changes in body fat and lean body mass during childhood and how age and gender affect these relationships. METHODS: This analysis used serial data on 494 white boys and girls who were aged 8 to 18 years and participating in the Fels Longitudinal Study (total 2319 observations). Total body fat (TBF), total body fat-free mass (FFM), and percentage of body fat (%BF) were determined by hydrodensitometry, and then BMI was partitioned into its fat and fat-free components: fat mass index (FMI) and FFM index (FFMI). We calculated predicted changes (Delta) in FMI, FFMI, and %BF for each 10-unit increase in BMI percentile using mixed-effects models. RESULTS: FFMI had a linear relationship with BMI percentile, whereas FMI and %BF tended to increase dramatically only at higher BMI percentiles. Gender and age had significant effects on the relationship between BMI percentile and FFMI, FMI, and %BF. Predicted Delta%BF for boys 13 to 18 years of age was negative, suggesting loss of relative fatness for each 10-unit increase in BMI percentile. CONCLUSIONS: In this longitudinal study of white children, FFMI consistently increased with BMI percentile, whereas FMI and %BF had more complicated relationships with BMI percentile depending on gender, age, and whether BMI percentile was high or low. Our results suggest that BMI percentile changes may not accurately reflect changes in adiposity in children over time, particularly among male adolescents and children of lower BMI.

Adolescent↗

PubMed2005

Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

Adolescent↗

PubMed2005

Heritability of age at menarche in girls from the Fels Longitudinal Study.

Menarche is the hallmark maturational event of female childhood. Many studies indicated a significant genetic contribution to the timing of the onset of menstruation, but most of these studies were limited by the use of retrospective data and by the use of data from only certain types of relatives (i.e., mothers and daughters, sisters, or twin sisters). The primary goal of this study was to use a modern maximum likelihood quantitative genetic method to estimate the heritability (h(2)) of age at menarche, using familial data collected over the course of the 74-year-old Fels Longitudinal Study. The secondary goal was to review earlier studies of the heritability of age at menarche. The study of the heritability of age at menarche presented here is unique for two reasons. First, because of the Fels Longitudinal Study's serial design, age-at-menarche data were collected prospectively from most participants. Second, because the Fels Longitudinal Study is a family study that has been conducted for decades, age-at-menarche data are available from many types of female relatives spanning multiple households and generations. The best-fitting and most parsimonious quantitative genetic model included provision for a secular decrease in age at menarche, and estimated the h(2) of age at menarche to be 0.49+/- 0.13 (95% confidence interval of h(2),=0.24-0.73). The results of this study are in general agreement with the findings of most previous studies of genetic influences on age at menarche, and suggest that it is reasonable to consider it well-established that approximately half the phenotypic variation among girls from developed nations in the timing of menarche is due to genetic factors.

Adolescent↗

PubMed2005

Quantitative genetic analysis of blood pressure response during the cold pressor test.

BACKGROUND: The genetic association between blood pressure (BP) at rest and during the cold pressor test (CPT) is not well characterized. The purpose of this study was to examine the genetic architecture of BP during the CPT, and to determine whether BP at rest and during the CPT share common genetic influences. METHODS: In 419 individuals distributed across four large families, variance components methods were used to estimate heritabilities of resting BP and CPT BP, along with genetic correlations among BP traits. The CPT consisted of immersion of the left foot in 4 degrees C water while the participant was supine. Blood pressure reactivity (DeltaBP) was defined as BP at 15 to 30 sec and 45 to 60 sec of foot immersion minus resting BP. RESULTS: Significant (P < .05) heritabilities were found for supine BP (h(2)(SBP) = 0.35), CPT BP (h(2)(SBP) = 0.27 and 0.33, h(2)(DBP) = 0.18 and 0.30), and DeltaSBP (h(2)(SBP) = 0.12 and 0.37) but not for DeltaDBP. Bivariate analyses detected significant (P < .05) genetic correlations between resting SBP and CPT SBP that were different from 0 and 1. Genetic correlations between resting DBP and CPT DBP were not significantly different from 1. Genetic correlations between resting SBP and DeltaSBP were not significant. CONCLUSIONS: Measures of BP at rest and during cold immersion are significantly influenced by additive genetic effects. These genetic influences are only partially shared between SBP at rest and SBP during cold immersion, suggesting that a somewhat different set of genes may influence SBP during cold immersion. Unique sets of genes also appear to influence DeltaSBP independent of those influencing resting SBP.

Adolescent↗

PubMed2004

Heritability of calcaneal quantitative ultrasound measures in healthy adults from the Fels Longitudinal Study.

Quantitative ultrasound (QUS) measurements of bone have been reported to predict osteoporotic fracture risk in postmenopausal women and older men. Although many studies have examined the heritability of bone mineral density (BMD), few studies have estimated the heritability of calcaneal QUS phenotypes. In the present study, we examined the genetic regulation of calcaneal QUS parameters in individuals from nuclear and extended families. The study population includes 260 men and 295 women aged 18-91 years (mean+/-SD: 46+/-16 years) who belong to 111 pedigrees in the Fels Longitudinal Study. Three measures of calcaneal structure were collected from both the right and left heel using the Sahara bone sonometer. These measures included broadband ultrasound attenuation (BUA), speed of sound (SOS), and the quantitative ultrasound index (QUI). We used a variance components based maximum likelihood method to estimate the heritability of QUS parameters while simultaneously adjusting for covariate effects. Additionally, we used bivariate extensions of these methods to calculate additive genetic and random environmental correlations among QUS measures. All phenotypes demonstrated statistically significant heritabilities (P<0.0000001). Heritabilities in the right heel (h2+/-SE) were h2=0.59+/-0.10 for BUA, h2=0.73+/-0.09 for SOS, and h2=0.72+/-0.09 for QUI. Similarly, heritabilities for the left heel were h2=0.52+/-0.10, h2=0.75+/-0.10, and h2=0.70+/0.10, respectively. There was evidence for significant genetic and environmental correlations among these six QUS measures. Combinations of QUS measures in the right and left heel demonstrated genetic correlations of 0.94-0.99 and all were significantly different from one indicating at least a partially unique genetic architecture for each of these measures. This study demonstrates that QUS measures of the calcaneus among healthy men and women are heritable, and there are large shared additive genetic effects among all of the traits examined.

Adolescent↗

PubMed2004

Fifty-year trends in serial body mass index during adolescence in girls: the Fels Longitudinal Study.

BACKGROUND: A decline in the age at menarche was recently reported for US girls. Although it is possible that this recent drop stems from the concurrent increase in childhood obesity, few longitudinal studies of growth and development have been undertaken to specifically address the temporal relation between growth, adiposity, and the age at menarche. OBJECTIVE: The objective was to simultaneously examine the effects of birth cohort (secular trend) and rate of maturation (age at menarche) on the timing and pattern of increases in body mass index (BMI) during adolescence in girls. DESIGN: We applied mixed-effects polynomial models to serial BMI data, spanning from 6 y before menarche to 6 y after menarche, obtained from 211 girls enrolled in the Fels Longitudinal Study. We examined the effects of birth cohort (defined as girls born 1929-1946, 1947-1964, and 1965-1983) and age at menarche (defined as < or =11.9 y, 12.0-13.1 y, and > or =13.2 y) on the magnitude and velocity of BMI during adolescence. RESULTS: BMI and BMI velocity in girls born after 1965 were significantly greater than those of girls of earlier birth cohorts, despite stability in the mean age at menarche. Although girls with early menarche tended to have significantly higher BMIs than did girls with average or later menarche, these differences did not emerge until after menarche. CONCLUSION: These data suggest that increases in relative weight are a consequence, rather than a determinant, of the age at menarche and that secular changes in BMI and in the mean age at menarche could be independent phenomena.

Adolescent↗

PubMed2004

Gene by smoking interaction: evidence for effects on low-density lipoprotein size and plasma levels of triglyceride and high-density lipoprotein cholesterol.

We seek to determine whether significant gene x smoking interaction effects exist on plasma triglyceride (TG) levels, HDL cholesterol (HDL-C) level, and median LDL particle diameter (LDL-MPD) in Mexican American families enrolled in the San Antonio Family Heart Study. The sample consisted of 1,392 individuals distributed in 42 extended pedigrees, ranging in age from 16 years to 92 years. Separate quantitative genetic analyses were carried out for TG and HDL-C level and LDL-MPD using a maximum-likelihood-based variance decomposition approach while simultaneously adjusting for age and sex. Initial heritability estimates demonstrated significant (p < 0.001) additive genetic contributions to all three traits (h2 range 0.50 - 0.54). To test for a gene x smoking interaction, we included in the model additional smoking-status-specific variance terms and a genetic correlation term between smokers and nonsmokers. Comparisons of nested models revealed significant evidence (p < 0.01) for a gene X smoking interaction effect on TG level and LDL-MPD and possible evidence for an effect on HDL-C level. These results indicate that the gene or suite of genes regulating each of these phenotypes is likely the same in smokers and non-smokers but that smoking may alter the expression of genes, particularly those influencing TG level and LDL-MPD.

Adolescent↗

PubMed2003

Development and validation of skinfold-thickness prediction equations with a 4-compartment model.

BACKGROUND: Skinfold-thickness measurements are commonly obtained for the indirect assessment of body composition. OBJECTIVE: We developed new skinfold-thickness equations by using a 4-compartment model as the reference. Additionally, we compared our new equations with the Durnin and Womersley and Jackson and Pollock skinfold-thickness equations to evaluate each equation's validity and precision. DESIGN: Data from 681 healthy, white adults were used. Percentage body fat (%BF) values were calculated by using the 4-compartment model. The cohort was then divided into validation and cross-validation groups. Equations were developed by using regression analyses and the 4-compartment model. All equations were then tested by using the cross-validation group. Tests for accuracy included mean differences, R(2), and Bland-Altman plots. Precision was evaluated by comparing root mean squared errors. RESULTS: Our new equations' estimated means for %BF in men and women (22.7% and 32.6%, respectively) were closest to the corresponding 4-compartment values (22.8% and 32.8%). The Durnin and Womersley equation means in men and women (20.0% and 31.0%, respectively) and the Jackson and Pollock mean in women (26.2%) underestimated %BF. All equations showed a tendency toward underestimation in subjects with higher %BF. Bland-Altman plots showed limited agreement between Durnin and Wormersley, Jackson and Pollock, and the 4-compartment model. Precision was similar among all the equations. CONCLUSIONS: We developed accurate and precise skinfold-thickness equations by using a 4-compartment model as the method of reference. Additionally, we found that the skinfold-thickness equations frequently used by clinicians and practitioners underestimate %BF.

Adipose Tissue↗

PubMed2003

Puberty and body composition.

Body composition during puberty is a marker of metabolic changes that occur during this period of growth and maturation, and, thus, holds key information regarding current and future health. During puberty, the main components of body composition (total body fat, lean body mass, bone mineral content) all increase, but considerable sexual dimorphism exists. Methods for measuring body composition (e.g. densitometry and dual-energy X-ray absorptiometry) and degree of maturity will be discussed in this review. Components of body composition show age-to-age correlations (i.e. 'tracking'), especially from adolescence onwards. Furthermore, adipose tissue is endocrinologically active and is centrally involved in the interaction between adipocytokines, insulin and sex-steroid hormones, and thus influences cardiovascular and metabolic disease processes. In conclusion, pubertal body composition is important, not only for the assessment of contemporaneous nutritional status, but also for being linked directly to the possible onset of chronic disease later in life and is, therefore, useful for disease risk assessment and intervention early in life.

Adolescent↗

PubMed2002

Genotype by smoking interaction for leptin levels in the San Antonio Family Heart Study.

Recent studies reported a marked inverse effect of smoking on serum levels of leptin (an adipocyte derived protein), offering a possible explanation for variation in body weight between smokers and non-smokers. The goal of this study was to examine the genetic architecture of the response to smoking in leptin levels using data from the San Antonio Family Heart Study. We employed a variance decomposition analysis using maximum likelihood methods to model genotype by smoking interactions for leptin levels, examined the impact of the exclusion of smokers in a subsequent linkage analysis, and incorporated the QTL identified in the linkage analysis in a model of genotype by smoking interaction. We found significant evidence (P = 0.001) for a genotype by smoking status interaction for serum leptin levels. In the subsequent linkage analysis with smokers excluded, we obtained a maximum LOD score of 3.1 (P = 0.00008) near D8S1102. Using this QTL in a model of genotype by smoking status interaction, we identified significant evidence for an interaction at this specific locus (P = 0.04). Given these results, we hypothesize that a quantitative trait locus in this vicinity of chromosome 8 may have a differential effect on the expression of leptin in smokers versus non-smokers.

Adult↗

PubMedDate not supplied

Recent decline in age at menarche: the Fels Longitudinal Study.

A number of recent reports suggest that the average age at menarche of US girls has declined over the past 20 years. Because the putative declines in the age at menarche are concurrent with increases in childhood body mass index (BMI), it has been suggested that these two trends may be causally linked. We examined differences in mean age of menarche in Fels Longitudinal Study girls who were born in six 10-year birth cohorts (1930s, 1940s, 1950s, 1960s, 1970s, and 1980s) and simultaneous cohort changes in mean BMI measured cross-sectionally at selected ages from 3-35 years (n = 371). Girls born in the 1980s had a mean age at menarche of 12.34 years, which was approximately 3-6 months earlier than that of girls born previously (P < 0.001). While the mean BMI values at ages 25 and 35 generally increased from the 1930s to the 1970s, the mean BMI during childhood and adolescence remained constant across the six birth cohorts. In summary, we found no evidence that the recent decline in the age at menarche in the Fels Longitudinal Study girls was reflected in concurrent increases in BMI at any point in childhood or adolescence. Conversely, girls born in the 1960s and 1970s have subsequently become heavier in young and mid-adulthood than were girls from earlier birth cohorts, without any concurrent change in the mean age at menarche over that time period. These two findings suggest that population-level shifts in BMI and the timing of menarche are largely independent, although sometimes coincident, processes.

Adolescent↗