External Validation of Equations that Use Demographic and Anthropometric Measurements to Predict Percent Body Fat.

OBJECTIVE: Numerous equation to predict percent body fat using demographics and anthropometrics have been published but external validation of these equations is limited. The objective of this study was to validate published equations that use anthropometrics for prediction of percent body fat using external data. METHODS: Data were from the Visceral Fat, Metabolic Rate, and Coronary Heart Disease Risk I (VIM I) Study and the Fels Longitudinal Study (Fels). VIM I was conducted in a subset of subjects from the CARDIA study and included black and white adults 28-40 years (n = 392). Fels consisted of white participants 8-88 years (n = 1,044). Percent body fat assessed by dual X-ray absorptiometry (DXA) in these two studies was compared to results calculated using 13 equations from Stevens et al. and nine other published equations. RESULTS: In general, the Stevens equations performed better than equations from other studies. For example, equation "I" in women in VIM I, Fels adults, and Fels youth, R2 estimates were 0.765, 0.757 and 0.789, respectively. In men the estimates were 0.702 in VIM I, 0.822 in Fels adults and 0.905 in Fels youth. None of the results from the nine published equations showed R2 this high in corresponding groups. CONCLUSIONS: Our results indicate that several of the Stevens equations have external validity superior to that of nine other published equations among varying age groups, genders and races.

The positive association of infant weight gain with adulthood body mass index has strengthened over time in the Fels Longitudinal Study.

BACKGROUND: Infant weight gain is positively related to adulthood body mass index (BMI), but it is unknown whether or not this association is stronger for individuals born during (compared with before) the obesity epidemic. OBJECTIVES: The aim of the study was to examine how the infant weight gain-adulthood BMI association might have changed across successive birth year cohorts spanning most of the 20th century. METHODS: The sample comprised 346 participants in the Fels Longitudinal Study. Confounder-adjusted regression models were used to test the associations of conditional weight-for-length Z-score, capturing weight change between ages 0-2 years, with young adulthood BMI and blood pressure, including cohort [1933-1949 {N = 137}, 1950-1969 {N = 108}, 1970-1997 {N = 101}] as an effect modifier. RESULTS: Conditional weight-for-length Z-score was positively related to adulthood BMI, but there was significant effect modification by birth year cohort such that the association was over two times stronger in the 1970-1997 cohort (ß 2.31; 95% confidence interval 1.59, 3.03) compared with the 1933-1949 (0.98; 0.31, 1.65) and 1950-1969 (0.87; 0.21, 1.54) cohorts. A similar pattern was found for systolic blood pressure. CONCLUSIONS: The infant weight gain-adulthood BMI association was over two times stronger among a cohort born during the obesity epidemic era compared with cohorts born earlier in the 20th century.

Body mass index associations between mother and offspring from birth to age 18: the Fels Longitudinal Study.

BACKGROUND: Parental obesity is a known determinant of childhood obesity. Previous research has shown a strong maternal influence on body mass index (BMI) during infancy and early childhood. OBJECTIVES: The purpose of this research was to investigate the BMI associations between mother and offspring from birth to age 18 years. METHODS: Participants were selected from the Fels Longitudinal Study. The current study sample includes 427 (215 mother/son and 212 mother/daughter) mother/child pairs. These pairs are repeatedly measured at multiple age groups in children, resulting in a total of 6,263 (3,215 mother/son, 3,048 mother/daughter) observations for data analysis. Inclusion criteria were children with measured height and weight for BMI collected at ages 0 to 18 years and their mother with BMI data. Maternal influences of BMI on offspring BMI from birth to early adulthood were analyzed by Spearman correlations and linear regression analyses. RESULTS: Mother/son BMI correlations became statistically significant (p ≤ 0.05) at age 5-6 years and were significant through puberty and into early adulthood at age 18 years. Mother/daughter correlations became significant at age 1.5 years and also continued through adolescence, puberty and early adulthood at age 18 years. Associations persisted after the study sample was grouped into life stages and adjusted for decade of birth and parity. CONCLUSIONS: The mother/daughter relationship was more strongly correlated than the mother/son relationship and also became statistically significant at an earlier age than boys.

Is infant body mass index associated with adulthood body composition trajectories? An exploratory analysis.

BACKGROUND: Infant body mass index (BMI) is increasingly used as a marker of obesity risk based on its association with young-adulthood BMI. OBJECTIVES: The aim of this study is to test the association of infant BMI with young-adulthood fat mass and fat-free mass, and how this association changes during advancing adulthood. METHODS: Body mass index Z-score at age 9 months was measured in 350 White, non-Hispanic Fels Longitudinal Study participants. This exposure was entered into multilevel models to test its association with trajectories describing 2665 BMI observations and 1388 observations of fat mass index (FMI, kg m-2 ) and fat-free mass index (FFMI, kg m-2 ) between ages 20 and 60 years. RESULTS: Partitioning young-adulthood BMI into its fat and fat-free components, infant BMI Z-score was associated with FFMI (ß = 0.745; 95% confidence interval = 0.367 to 1.124) but not FMI (0.528; -0.055 to 1.110) at age 20 years. Greater infant BMI Z-score was associated with slower age-related increases in all outcomes, such that (looking at 10-year intervals) only FFMI at age 30 years was related to infant BMI Z-score (0.338; 0.119, 0.557). CONCLUSIONS: Focus on infant BMI reduction for adulthood obesity prevention warrants caution as high infant BMI values are associated with greater lean mass, which is protective against ageing changes.

Sex differences in the rate of abdominal adipose accrual during adulthood: the Fels Longitudinal Study.

OBJECTIVES: The purpose of this analysis was to evaluate sex differences in the rate of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) accrual in adults. Secondary analyses examined differences in the rate of VAT and SAT accrual in premenopausal, perimenopausal and postmenopausal women. SUBJECTS/METHODS: Participants were 472 (60% female) non-Hispanic whites and aged 18-84 years at baseline in whom abdominal VAT and SAT were assessed using multiple-image magnetic resonance imaging at two time points, with an average follow-up of 7.3±2.6 years. Linear regression models were used to examine the effects of sex, baseline age and their interaction on rate of change per year in body composition measures (ΔBMI, ΔVAT and ΔVAT/SAT ratio (ΔVSR)) independent of baseline body composition measures, visit year, income, marital status, physical activity, smoking and alcohol intake. Secondary analyses examined differences in the rate of fat change by menopausal status (premenopausal, perimenopausal, postmenopausal). RESULTS: Levels of body mass index (BMI), VAT and VSR all increased over the 7-year period on average (P<0.001); however, the change in BMI (mean ΔBMI=+0.5%) was far smaller than for VAT (mean ΔVAT=+6.8%), SAT (mean ΔSAT=+2.4%) and VSR (mean ΔVSR=+3.6%). ΔBMI, ΔVAT and ΔSAT decreased linearly with age in both sexes (P<0.01), such that older individuals had lower rates of BMI, VAT and SAT gain, and this deceleration in BMI, VAT and SAT accrual was greater in men than women (P for interaction <0.05). ΔVSR did not vary with age in either sex but remained higher in men than women throughout adulthood. There were no differences in rate of weight or fat gain by menopausal status after adjustment for age. CONCLUSIONS: Men and women continue to accrue abdominal adiposity with age, but the rate of weight and fat gain decreases over time, particularly in men.

How much do children's body mass indices change over intervals of 6-12 months? Statistics from before and during the obesity epidemic.

BACKGROUND: Researchers need to evaluate changes in children's body mass index (BMI) over periods of 6 or 12 months, yet reference statistics are limited for change in BMI. OBJECTIVES: We aim to estimate the distribution of changes in children's BMIs over periods of 6 and 12 months. METHODS: We analyze data on two cohorts of children in the Fels Longitudinal Study: an older cohort born 1946-1970 and a recent cohort born 1971-1995. Between ages 3 and 18 years, we calculate changes in BMI over intervals of 6 and 12 months. For each age, sex and cohort, we estimate the mean, standard deviation, skewness, kurtosis and percentiles of change in BMI. RESULTS: Median BMI growth peaks around age 12-13 years for girls and 13-15 years for boys. Large BMI gains are common in adolescence, and BMI losses are not uncommon at any age. Percentiles of BMI change are quite dispersed, especially for girls and especially in adolescence. In the recent cohort, the adiposity rebound is earlier and BMI gains are larger, especially at the high percentiles. CONCLUSIONS: Researchers can use these estimates to evaluate data quality, evaluate effect sizes and calculate the sample size needed to detect an effect.

Stronger influence of maternal than paternal obesity on infant and early childhood body mass index: the Fels Longitudinal Study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Excessive early childhood adiposity is a prevalent and increasing concern in many parts of the world. Parental obesity is one of the several factors previously associated with infant and early childhood weight, length and adiposity. Parental obesity represents a surrogate marker of the complex interplay among genetic, epigenetic and shared environmental factors, and is potentially modifiable. The relative contributions of maternal and paternal body mass index (BMI) to infant and early childhood growth, as well as the timing of such effects, have not been firmly established. WHAT THIS STUDY ADDS: Utilizing serial infant measurements and growth curve modelling, this is the largest study to fully characterize and formally compare associations between maternal and paternal BMI and offspring growth across the entire infancy and early childhood period. Maternal obesity is a stronger determinant of offspring BMI than paternal obesity at birth and from 2 to 3 years of age, suggesting that prevention efforts focused particularly on maternal lifestyle and BMI may be important in reducing excess infant BMI. The observation that maternal BMI effects are not constant, but rather present at birth, wane and re-emerge during late infancy, suggests that there is a window of opportunity in early infancy when targeted interventions on children of obese mothers may be most effective. BACKGROUND/OBJECTIVE: Parental obesity influences infant body size. To fully characterize their relative effects on infant adiposity, associations between maternal and paternal body mass index (BMI) category (normal: ≤25 kg m(-2) , overweight: 25 - <30 kg m(-2) , obese: ≥30 kg m(-2) ) and infant BMI were compared in Fels Longitudinal Study participants. METHODS: A median of 9 serial weight and length measures from birth to 3.5 years were obtained from 912 European American children born in 1928-2008. Using multivariable mixed effects regression, contributions of maternal vs. paternal BMI status to infant BMI growth curves were evaluated. Cubic spline models also included parental covariates, infant sex, age and birth variables, and interactions with child's age. RESULTS: Infant BMI curves were significantly different across the three maternal BMI categories (Poverall < 0.0001), and offspring of obese mothers had greater mean BMI at birth and between 1.5 and 3.5 years than those of over- and normal weight mothers (P ≤ 0.02). Average differences between offspring of obese and normal weight mothers were similar at birth (0.8 kg m(-2) , P = 0.0009) and between 2 and 3.5 years (0.7-0.8 kg m(-2) , P < 0.0001). Infants of obese fathers also had BMI growth curves distinct from those of normal weight fathers (P = 0.02). Infant BMI was more strongly associated with maternal than paternal obesity overall (P < 0.0001); significant differences were observed at birth (1.11 kg m(-2) , P = 0.006) and from 2 to 3 years (0.62 kg m(-2) , P3 years = 0.02). CONCLUSION: At birth and in later infancy, maternal BMI has a stronger influence on BMI growth than paternal BMI, suggesting weight control in reproductive age women may be of particular benefit for preventing excess infant BMI.

Genome-wide linkage scan for quantitative trait loci underlying normal variation in heel bone ultrasound measures.

Quantitative ultrasound (QUS) traits are correlated with bone mineral density (BMD), but predict risk for future fracture independent of BMD. Only a few studies, however, have sought to identify specific genes influencing calcaneal QUS measures. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing normal variation in QUS traits. QUS measures were collected from a total of 719 individuals (336 males and 383 females) from the Fels Longitudinal Study who have been genotyped and have at least one set of QUS measurements. Participants ranged in age from 18.0 to 96.6 years and were distributed across 110 nuclear and extended families. Using the Sahara ® bone sonometer, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI) were collected from the right heel. Variance components based linkage analysis was performed on the three traits using 400 polymorphic short tandem repeat (STR) markers spaced approximately 10 cM apart across the autosomes to identify QTL influencing the QUS traits. Age, sex, and other significant covariates were simultaneously adjusted. Heritability estimates (h²) for the QUS traits ranged from 0.42 to 0.57. Significant evidence for a QTL influencing BUA was found on chromosome 11p15 near marker D11S902 (LOD = 3.11). Our results provide additional evidence for a QTL on chromosome 11p that harbors a potential candidate gene(s) related to BUA and bone metabolism.

Patterns of linear growth and skeletal maturation from birth to 18 years of age in overweight young adults.

OBJECTIVE: To estimate differences in skeletal maturity and stature from birth to age 18 years between individuals who are overweight vs normal weight in young adulthood. PATIENTS AND METHODS: Weight, length and height, and relative skeletal age (skeletal-chronological age) were assessed annually from birth to age 18 years in 521 subjects (255 women) in the Fels Longitudinal Study who were overweight or obese (body mass index (BMI) >25 kg m(-2), n=131) or normal weight (n=390) in young adulthood (18-30 years). Generalized estimating equations were used to test for skeletal maturity and stature differences by young adult BMI status. RESULTS: Differences in height increased during puberty, being significant for girls at ages 10 to 12 years, and for boys at ages 11 to 13 years (P-values<0.001), with overweight or obese adults being ∼3 cm taller at those ages than normal weight adults. These differences then diminished so that by age 18 years, overweight or obese adults were not significantly different in stature to their normal weight peers. Differences in skeletal maturity were similar, but more pervasive; overweight or obese adults were more skeletally advanced throughout childhood. Skeletal maturity differences peaked at chronological age 12 in boys and 14 in girls (P-values<0.001), with overweight or obese adults being ∼1 year more advanced than normal weight adults. CONCLUSIONS: This descriptive study is the first to track advanced skeletal maturity and linear growth acceleration throughout infancy, childhood and adolescence in individuals who become overweight, showing that differences occur primarily around the time of the pubertal growth spurt. Increased BMI in children on a path to becoming overweight adults precedes an advancement in skeletal development and subsequently tall stature during puberty. Further work is required to assess the predictive value of accelerated pubertal height growth for assessing obesity risk in a variety of populations.

Longitudinal changes in calcaneal quantitative ultrasound measures during childhood.

UNLABELLED: This longitudinal study examined how calcaneal quantitative ultrasound (QUS) measures change during childhood while taking into account skeletal maturation, body mass index (BMI), and physical activity. The study reported sex differences in QUS growth curves and an inverse relationship between BMI and speed of sound (SOS) measures. INTRODUCTION: The aim of this study was to examine how calcaneal QUS parameters change over time during childhood and to determine what factors influence these changes. METHODS: The study sample consisted of a total of 192 Caucasian children participating in the Fels Longitudinal Study. A total of 548 calcaneal broadband ultrasound attenuation (BUA) and SOS observations were obtained between the ages of 7.6 and 18 years. The best fitting growth curves were determined using statistical methods for linear mixed effect models. RESULTS: There are significant sex differences in the pattern of change in QUS parameters (p < 0.05). The relationship between QUS measures and skeletal age is best described by a cubic growth curve in boys and a linear pattern among girls. Boys experience their most rapid growth in BUA and SOS in early and late adolescence, while girls experience constant growth throughout childhood. Adiposity levels were significantly associated with the changes in SOS among boys (p < 0.001) and girls (p < 0.01), indicating that children with higher BMI are likely to have lower SOS over time compared to children with lower BMI. For girls, physical activity levels showed positive associations with changes in QUS measures (p < 0.05). CONCLUSION: This study documents significant sex differences in the pattern of change in QUS measures over childhood and adolescence. Our study also shows significant influences of adiposity and physical activity on the pattern of change in QUS measures during childhood.

Sleep disturbance in relation to health-related quality of life in adults: the Fels Longitudinal Study.

OBJECTIVE: Sleep disturbances are prevalent problems in the general population. Symptoms of insomnia can impact various physical and mental conditions. Furthermore, sleep disturbances may worsen the quality of life independently of co-occurring medical conditions. In this study, we examined the relationships between self-reported sleep disturbance symptoms and health-related quality of life measures in the Fels Longitudinal Study. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 397 adults (175 men and 222 women) aged 40 years and older were included in the present study. MEASUREMENTS: Three self-reported sleep disturbance measures (difficulty falling asleep, nocturnal awakenings and maintaining sleep, and daytime tiredness) were collected between 2003 and 2006. Health-related quality of life measures were assessed using the Medical Outcomes Survey Short Form (SF)-36. Socio-demographic status (marital status, employment status, and education) and current medical conditions were collected from participants during study visits. RESULTS: Individuals who reported frequent sleep disturbances showed significantly worse quality of life on all SF-36 subscales examined. The odds ratio (OR) ranged from 1.71 to 18.32 based on symptoms of insomnia across seven SF-36 domains in analyses adjusted for significant covariates influencing quality of life. Participants with severe sleep disturbances (both sleep problems and daytime impairment) showed generally higher odds of reporting poor SF-36 scores (adjusted ORs; 5.88 - 17.09) compared to participants with no problems. CONCLUSION: Sleep disturbance is comprehensively and independently associated with poor health-related quality of life in middle-aged and older adults.

Validity of a new automated software program for visceral adipose tissue estimation.

INTRODUCTION: Given the considerable time and research cost of analyzing biomedical images to quantify adipose tissue volumes, automated image analysis methods are highly desirable. Hippo Fat is a new software program designed to automatically quantify adipose tissue areas from magnetic resonance images without user inputs. Hippo Fat has yet to be independently validated against commonly used image analysis software programs. OBJECTIVE: Our aim was to compare estimates of VAT (visceral adipose tissue) and SAT (subcutaneous adipose tissue) using the new Hippo Fat software against those from a widely used, validated, computer-assisted manual method (slice-O-matic version 4.2, Tomovision, Montreal, CA, USA) to assess its potential utility for large-scale studies. METHODS: A Siemens Magnetom Vision 1.5-T whole-body scanner and a T1-weighted fast-spin echo pulse sequence were used to collect multiple, contiguous axial images of the abdomen from a sample of 40 healthy adults (20 men) aged 18-77 years of age, with mean body mass index of 29 kg/m(2) (range=19-43 kg/m(2)). RESULTS: Hippo Fat provided estimates of VAT and SAT that were highly correlated with estimates using slice-O-matic (R (2)>0.9). Average VAT was 9.4% lower and average SAT was 3.7% higher using Hippo Fat compared to slice-O-matic; the overestimation of SAT tended to be greater among individuals with greater adiposity. Individual-level differences for VAT were also substantial; Hippo Fattrade mark gave estimates of VAT ranging from 1184 cm(3) less to 566 cm(3) more than estimates for the same person using slice-O-matic. CONCLUSION: Hippo Fat provides a rapid method of quantifying total VAT, although the method does not provide estimates that are interchangeable with slice-O-matic at either the group (mean) or individual level.

Unique and common genetic effects between bone mineral density and calcaneal quantitative ultrasound measures: the Fels Longitudinal Study.

INTRODUCTION: Areal bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) measures are correlated, and both traits predict osteoporotic fracture risk independently. However, few studies have examined whether common genetic effects (i.e., pleiotropy) exist between these traits in extended families. In this study, we estimated the additive genetic correlation and random environmental correlation between BMD measured at various skeletal sites and calcaneal QUS measures. METHODS: Our sample included 537 adults (251 men and 286 women) from 110 families participating in the Fels Longitudinal Study. Total hip, femoral neck, lumbar spine, and total body BMD were measured using dual energy X-ray absorptiometry. Three measures of calcaneal structure--broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI)--were collected from the non-dominant heel using the Sahara sonometer. Applying a variance components-based maximum likelihood method, we estimated the heritability of each trait and estimated the genetic and environmental correlations between the different BMD and QUS measures. RESULTS: Heritability estimates were significant for all measures of BMD and QUS ranging from 0.55 to 0.78. Significant non-zero genetic correlations were found between the different BMD and QUS measures. All genetic correlations were also significantly different from 1. Genetic correlations between total hip BMD and each of the QUS measures were 0.63 with BUA, 0.50 with SOS, and 0.56 with QUI. For femoral neck BMD, genetic correlations were similar to those between total hip BMD and QUS measures. Genetic correlations between BMD of the lumbar spine and QUS measures ranged from 0.34 to 0.38, and those between total body BMD and QUS measures, from 0.51 to 0.54. In contrast, all random environmental correlations were not significantly different from zero. CONCLUSION: This study demonstrates that BMD and calcaneal QUS measures among healthy men and women are significantly heritable and are, in part, jointly influenced by a common set of underlying genes. Additionally, this study also provides evidence for a unique set of genes that independently influences each individual trait.

Quantitative genetic analysis of blood pressure reactivity to orthostatic tilt using principal components analysis.

Blood pressure (BP) reactivity to orthostatic tilt may be predictive of cardiovascular disease. However, the genetic and environmental influences on BP reactivity to tilt have not been well examined. Identifying different influences on BP at rest and BP during tilt is complicated by the intercorrelation among multiple measurements. In this study, we use principal components analysis (PCA) to reduce multivariate BP data into components that are orthogonal. The objective of this study is to characterize and examine the genetic architecture of BP at rest and during head-up tilt (HUT). Specifically, we estimate the heritability of individual BP measures and three principal components (PC) derived from multiple BP measurements during HUT. Additionally, we estimate covariate effects on these traits. The study sample consisted of 444 individuals, distributed across four large families. HUT consisted of 70 degrees head-up table tilting while strapped to a tilt table. BP reactivity (deltaBP) was defined as BP during HUT minus BP while supine. Three PC extracted from the PCA were interpreted as 'general BP' (PC1), 'pulse pressure' (PC2) and 'BP reactivity' (PC3). Variance components methods were used to estimate the heritabilities of resting BP, HUT BP, deltaBP, as well as the three BP PC. Significant (P<0.05) heritabilities were found for all BP measurements, except for systolic deltaBP at 1 and 3 min, and diastolic deltaBP at 2 min. Significant genetic effects were also found for the three PC. Each of these orthogonal components is significantly influenced by somewhat different sets of covariates.

Lipids, lipoproteins, lifestyle, adiposity and fat-free mass during middle age: the Fels Longitudinal Study.

INTRODUCTION: Although lipid profiles tend to worsen with age, it is not fully known if such age-related changes are influenced primarily by body composition and lifestyle or by other aspects of aging. OBJECTIVE: We investigated the extent to which the fat and fat-free components of body mass index (BMI) and lifestyle factors influence patterns of change in lipids independent of age. DESIGN: Serial data were analyzed using sex-specific longitudinal models. These models use serial data from individuals to assume a general pattern of change over time, while allowing baseline age and the rate of change to vary among individuals. SUBJECTS: Serial data were obtained from 940 examinations of 269 healthy white participants (126 men, 143 women), aged 40-60 years, in the Fels Longitudinal Study. MEASUREMENTS: Measurements included age, the fat (FMI) and fat-free mass (FFMI) components of BMI, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), triglycerides (TG), total cholesterol (TC), fasting glucose and insulin, physical activity, alcohol use and smoking, and women's menopausal status and estrogen use. RESULTS: In both sexes, increased FMI was significantly associated with increased LDL-C, TG and TC, and decreased HDL-C. Increased FFMI was significantly related to decreased HDL-C and increased TG. Independent age effects remained significant only for LDL-C and TC in men and TC in women. Increased insulin was significantly related to increased TG in women. Moderate alcohol consumption was associated with higher HDL-C in men. Physical activity lowered male LDL-C and TC levels, and increased female HDL-C levels. Menopause was associated with increases in LDL-C. Premenopausal women not using estrogen had significantly lower HDL-C, TG, and TC than postmenopausal women taking estrogen. CONCLUSIONS: (1) Age is an important independent predictor for LDL-C and TC in men, and TC in women, but it is not as influential as body composition and lifestyle on HDL-C and TG in men and women, and LDL-C in women. (2) Increasing FMI is the major contributor to elevated TC, LDL-C and TG levels, and decreased HDL-C levels in men and women. (3) FFMI significantly influences HDL and TG levels in both sexes. (4) Maintaining a lower BMI via a reduced fat component may be more beneficial in lowering CVD risks than other factors.

Bone mineral density reference standards in adult baboons (Papio hamadryas) by sex and age.

Osteoporosis is a progressive condition involving structural deterioration of bone tissue, leading to skeletal fragility and an increased susceptibility to fractures due to low bone mass and high rates of bone turnover. Areal bone mineral density (aBMD) serves as the most reliable predictor of susceptibility to osteoporotic fracture. The development of animal models, including Old World Monkeys, has been essential to studies of bone mineral density. These animals, including the baboon, exhibit many biological similarities with our own species relevant to the variation in age-related changes and pathology in bone that may make them an excellent model for studies of skeletal structure and maintenance in humans. The baboon has been shown to exhibit extensive biological similarities to humans regarding skeletal biology, but little is known about the range of normal variation in skeletal traits, such as bone mineral density, in this species. Our data, collected on baboons (Papio hamadryas) that are part of a large breeding colony at the Southwest Foundation for Biomedical Research and the Southwest National Primate Research Center (San Antonio, TX), involve 466 females and 210 males, ranging in age from 5.5 to 30 years. Student's t tests, bivariate correlations, and likelihood ratio tests show sex and age effects at all spinal sites. Age effects are minimal or absent in the forearm sites. This study is the first to characterize normal variation in aBMD in baboons, to assess the effect of age and sex on this variation, and to compare this variation to those data currently available from experimental control animals. As such, it provides much-needed reference standards that will allow researchers to evaluate the status of their animals in cross-sectional studies and more fully assess the meaning of aBMD changes in longitudinal studies.

Does accounting for mitochondrial genetic variation improve the fit of genetic models?

We describe a simple variance component model for estimating the effect of mitochondrial DNA (mtDNA) inheritance on quantitative trait variation. The model is applied to quantitative trait Q5 in the simulated general population data from Genetic Analysis Workshop (GAW) 12. Although the mitochondrial effect on Q5 is small (5.3%) and the power of the method to detect the effect is correspondingly low, analysis over the available population replicates demonstrates that the effect of maternal relatedness can be detected and estimated accurately.

Plasma levels of extracellular superoxide dismutase in an Australian population: genetic contribution to normal variation and correlations with plasma nitric oxide and apolipoprotein A-I levels.

Extracellular superoxide dismutase (EC-SOD) is a major superoxide scavenger and may be important to normal vascular function and cardiovascular health. We analyzed family data from 610 healthy Australians to detect and quantify the effects of genes on normal variation in plasma levels of EC-SOD and to test for pleiotropy with plasma nitric oxide (NO) and apolipoprotein A-I (apoA-I). Using maximum-likelihood-based variance decomposition methods, we determined that sex, age, and plasma levels of HDL cholesterol, apoA-I, and creatinine accounted for 38.6% of the variance in plasma EC-SOD levels and that additive genes accounted for 35% (P<0.00002). Multivariate analyses of plasma levels of EC-SOD, NO(x) (a measure of basal NO production), and apoA-I detected significant genetic correlations, indicating pleiotropy between EC-SOD and apoA-I (genetic correlation [rho(G)]=-0.45) and between NO(x) and apoA-I (rho(G)=0.58) but not between EC-SOD and NO(x). Genes shared by EC-SOD and apoA-I account for 20% of the genetic variance and, respectively, 7% and 9% of the phenotypic variance in both traits. Shared genes also account for >33% of the genetic variance and 5% and 15% of the respective phenotypic variance in NO(x) and apoA-I. In healthy individuals, over a third of the variance in EC-SOD plasma levels is due to the additive effects of genes. Some genes influence EC-SOD and apoA-I levels. The same is true of NO(x) and apoA-I but not of EC-SOD and NO(x). These patterns of pleiotropy can guide subsequent attempts to identify the genes and physiological mechanisms underlying them.

Genetic analysis of personality traits and alcoholism using a mixed discrete continuous trait variance component model.

Bivariate analyses can improve power to detect linkage. This paper describes one application of a bivariate variance component method for estimating joint likelihoods of a continuous and a discrete trait. This method is applied to the Collaborative Study on the Genetics of Alcoholism data set to investigate the relationship between personality traits derived from the tridimensional personality questionnaire (TPQ) and alcoholism. The results indicate that the novelty-seeking subscale of the TPQ and alcoholism share a strong and significant genetic correlation (rho G = 0.83) and modest environmental correlation (rho E = 0.31). When both traits are considered jointly in a multipoint linkage model compared with the alcoholism trait alone, there is an improvement in the ability to detect and localize a quantitative trait locus on chromosome 4.

Social support and adverse pregnancy outcome in a high-risk population.

Low birth weight is a significant health problem in the United States, particularly among poor women. By combining traditional predictors of birth weight with social support indicators, we were able to substantially improve the discrimination between the highest birth weight quartile from the lowest among high-risk gravidae receiving first time prenatal care at the Albany, New York, County Department of Health. The impact of traditional predictors and social support indicators varied considerably between African-American and white women. Providers of care to poor women can utilize this information to maximize the likelihood of a good birth outcome.