Common genetic and environmental factors among craniofacial traits in Belgian nuclear families: Comparing skeletal and soft-tissue related phenotypes

The major objective of this study was to determine the possible effects of common genetic and environmental factors among 18 craniofacial anthropometric traits, with special attention to the differences between skeletal and soft-tissue related phenotypes. The studied sample consisted of 122 nuclear families living in Brussels and included 251 males and 258 females aged from 13 to 72 years. Univariate and bivariate quantitative genetic analyses were performed using a variance components procedure implemented in SOLAR software.All phenotypes were significantly influenced by additive genetic factors with heritability estimates ranging from 0.46 (nose height) to 0.72 (external biocular breadth). Sex, age and their interactions explained 7-46% of the total phenotypic variance of the traits. Bivariate analysis revealed that several traits share a common genetic and/or environmental basis while other traits show genetic and environmental independence from one another. More and greater genetic and environmental correlations were observed among skeletal phenotypes, than among soft-tissue traits and between both categories. Apart from the tissue composition, other characteristics of the craniofacial morphology such as the orientation (e.g. heights, breadths) have shown to be important factors in determining pleiotropy and common environmental effects between some pairs of traits. In conclusion, the results confirm that overall head configuration is largely determined by additive genetic effects, and that common genetic and environmental factors affecting craniofacial size and shape are stronger for the skeletal traits than for the soft-tissue traits.     

学龄双生子儿童头面部特征的遗传学分析

为探讨遗传与环境因素对学龄双生子儿童头面部特征的影响, 对呼和浩特市和包头市7-12岁369对双生子儿童(同卵180对, 同性别异卵141对, 异性别异卵48对)的16项头面部指标进行活体测量。采用通径分析方法, 用Mx软件拟合最佳结构方程模型, 计算各指标遗传与环境方差组分, 分析年龄、性别的作用。结果发现, 校正年龄后, 头部指标中头围的遗传度(男66%, 女66%)较高; 面部指标中, 容貌面高的遗传度(男73%, 女84%)最高, 其次为鼻宽(男57%, 女67%)、眼内角间宽(男57%, 女50%)和额最小宽(男50%, 女50%); 头长(男64%, 女25%)、头宽(男26%, 女82%)、眼外角间宽(男76%, 女34%)和容貌耳长(男23%, 女70%)的遗传度存在一定的性别差异。表明遗传因素与环境因素对学龄双生子儿童的头面部发育均有一定影响, 其中遗传因素对男女头围及容貌面高、男性头长和眼外角间宽、女性头宽、鼻宽、口宽、容貌耳长的影响相对较大。     

Biosocial covariates of adult male body mass index in Central India

Body mass index (BMI) is the 'measuring rod' of nutritional status. This study investigates the type and extent of correlation between adult male BMI and socioeconomic, cultural and bio-demographical variables using data from 11,496 individuals from 38 districts of Central India. For each individual, stature, body weight and sitting height data were collected, their Cormic index and BMI computed, and averages for each district calculated. Mean BMI was found to be lowest for the population of Tikamgarh (17.90+/-1.91 kg m(-2)) and highest for that of Durg district (19.33+/-2.16 kg m(-2)), whereas the mean BMI for the total population of Central India was 18.67+/-2.18 kg m(-2), which is lower than that of well-to-do individuals in India as a whole. The F ratio indicates that there is inter-district variation in anthropometric characteristics of populations. District-wise biosocial indicators were obtained, namely population density per square kilometre, percentage urban population, percentage of population that is of scheduled caste/tribe, sex ratio, average rural population per PHC/CHC (primary or community health centre), literacy rate, life expectancy, total fertility rate, infant mortality rate, gender development index and human development index. Most of these variables were found to be significantly correlated with each other, but BMI was only significantly correlated with three of them, viz. gender development index (R2=0.211), life expectancy (R2=0.130) and infant mortality rate (R2=0.128). Gender development index and life expectancy were positively correlated with BMI, whereas infant mortality rate was negatively correlated. It is concluded that if BMI increases then life expectancy will also increase. Thus better nutritional status may be a helpful tool for reducing infant mortality rate, which is an indicator of socioeconomic status, health condition, health care and ultimately overall development of a region or population.     

Maximum likelihood estimation of human craniometric heritabilities

This study presents univariate narrow-sense heritability estimates for 33 common craniometric dimensions, calculated using the maximum likelihood variance components method on a skeletal sample of 298 pedigreed individuals from Hallstatt, Austria. Quantitative genetic studies that use skeletal cranial measurements as a basis for inferring microevolutionary processes in human populations usually employ heritability estimates to represent the genetic variance of the population. The heritabilities used are often problematic: most come from studies of living humans, and/or they were calculated using statistical techniques or assumptions violated by human groups. Most bilateral breadth measures in the current study show low heritability estimates, while cranial length and height measures have heritability values ranging between 0.102-0.729. There appear to be differences between the heritabilities calculated from crania and those from anthropometric studies of living humans, suggesting that the use of the latter in quantitative genetic models of skeletal data may be inappropriate. The univariate skeletal heritability estimates seem to group into distinct regions of the cranium, based on their relative values. The most salient group of measurements is for the midfacial/orbital region, with a number of measures showing heritabilities less than 0.30. Several possible reasons behind this pattern are examined. Given the fact that heritabilities calculated on one population should not be applied to others, suggestions are made for the use of the data presented.     

Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage.

The aim of this study was to estimate the heritability of and environmental contributions to skeletal muscle phenotypes (appendicular lean mass and calf muscle cross-sectional area) in subjects of African descent and to determine whether heritability estimates are impacted by sex or age. Body composition was measured by dual-energy X-ray absorptiometry and computed tomography in 444 men and women aged 18 yr and older (mean: 43 yr) from eight large, multigenerational Afro-Caribbean families (family size range: 21-112). Using quantitative genetic methods, we estimated heritability and the association of anthropometric, lifestyle, and medical variables with skeletal muscle phenotypes. In the overall group, we estimated the heritability of lean mass and calf muscle cross-sectional area (h(2) = 0.18-0.23, P < 0.01) and contribution of environmental factors to these phenotypes (r(2) = 0.27-0.55, P < 0.05). In our age-specific analysis, the heritability of leg lean mass was lower in older vs. younger individuals (h(2) = 0.05 vs. 0.23, respectively, P = 0.1). Sex was a significant covariate in our models (P < 0.001), although sex-specific differences in heritability varied depending on the lean mass phenotype analyzed. High genetic correlations (rho(G) = 0.69-0.81; P < 0.01) between different lean mass measures suggest these traits share a large proportion of genetic components. Our results demonstrate the heritability of skeletal muscle traits in individuals of African heritage and that heritability may differ as a function of sex and age. As the loss of skeletal muscle mass is related to metabolic abnormalities, disability, and mortality in older individuals, further research is warranted to identify specific genetic loci that contribute to these traits in general and in a sex- and age-specific manner.     

Heritability of phenotypic udder traits to improve resilience to mastitis in Texel ewes

There are no estimates of the heritability of phenotypic udder traits in suckler sheep, which produce meat lambs, and whether these are associated with resilience to mastitis. Mastitis is a common disease which damages the mammary gland and reduces productivity. The aims of this study were to investigate the feasibility of collecting udder phenotypes, their heritability and their association with mastitis in suckler ewes. Udder and teat conformation, teat lesions, intramammary masses (IMM) and litter size were recorded from 10 Texel flocks in Great Britain between 2012 and 2014; 968 records were collected. Pedigree data were obtained from an online pedigree recording system. Univariate quantitative genetic parameters were estimated using animal and sire models. Linear mixed models were used to analyse continuous traits and generalised linear mixed models were used to analyse binary traits. Continuous traits had higher heritabilities than binary with teat placement and teat length heritability (h²) highest at 0.35 (SD 0.04) and 0.42 (SD 0.04), respectively. Udder width, drop and separation heritabilities were lower and varied with udder volume. The heritabilities of IMM and teat lesions (sire model) were 0.18 (SD 0.12) and 0.17 (SD 0.11), respectively. All heritabilities were sufficiently high to be in a selection programme to increase resilience to mastitis in the population of Texel sheep. Further studies are required to investigate genetic relationships between traits and to determine whether udder traits predict IMM, and the potential benefits from including traits in a selection programme to increase resilience to chronic mastitis.     

Traditional occupations and nutritional adaptation among Central Indian caste populations

The socioeconomic milieu has benefits and drawbacks for determining level of nutrition. The Indian population provides an excellent example of nutrition-driven adaptation. The present paper deals with the relationship between BMI (body mass index) and traditional occupation and process of adaptation among adult males of Central India. Anthropometric data collected by the Anthropological Survey of India on stature, sitting height and weight of 6663 adult males belonging to 22 castes were used for computation of BMI and Cormic index. The caste groups earning their living as labourers are found to be shortest (157.4+/-6.5 cm), and the caste group practising priesthood are tallest (168.6+/-6.6 cm). The prevalence of chronic energy deficiency is found to be highest (72%) among castes earning their living as daily wage labourers. The ANOVA on Cormic index and BMI suggests that people within the same occupational group are more homogeneous than those from different occupational groups. The t test also supports the homogeneity of the same occupational group.     

Age-stratified heritability estimation in the Framingham Heart Study families

The Framingham Heart Study provides a unique source of longitudinal family data related to CVD risk factors. Age-stratified heritability estimates were obtained over three age groups (31-49 years, 50-60 years, and 61-79 years), reflecting the longitudinal nature of the data, for four quantitative traits. Age-adjusted heritability estimates were obtained at a single common time point for the same four quantitative traits. The importance of these groups is that they consist of the same individuals. The highest age-stratified heritability estimate (h2 = 0.88 (+/- 0.06)) was for height in the model adjusting for gender over all three age groups. SBP gave the lowest heritability estimate (h2 = 0.15 (+/- 0.11)) for the 70 age group in the model adjusting for gender, height, BMI, smoker, and drinker. BMI had slightly higher estimates (h2 = 0.64 (+/- 0.11)) in the 40 age group than previously published. The highest age-adjusted heritability estimate (h2 = 0.90 (+/- 0.06)) was for height in the model adjusting for gender. SBP gave the lowest heritability estimate (h2 = 0.38 (+/- 0.09)) for unadjusted model. These results indicate that some common, complex traits may vary little in their genetic architecture over time and suggest that a common set of genes may be contributing to observed variation for these longitudinally collected phenotypes.     

The genetic dissection of complex traits in a founder population

We estimated broad heritabilities (H(2)) and narrow heritabilities (h(2)) and conducted genomewide screens, using a novel association-based mapping approach for 20 quantitative trait loci (QTLs) among the Hutterites, a founder population that practices a communal lifestyle. Heritability estimates ranged from.21 for diastolic blood pressure (DBP) to.99 for whole-blood serotonin levels. Using a multipoint method to detect association under a recessive model we found evidence of major QTLs for six traits: low-density lipoprotein (LDL), triglycerides, lipoprotein (a) (Lp[a]), systolic blood pressure (SBP), serum cortisol, and whole-blood serotonin. Second major QTLs for Lp(a) and for cortisol were identified using a single-point method to detect association under a general two-allele model. The heritabilities for these six traits ranged from.37 for triglycerides to.99 for serotonin, and three traits (LDL, SBP, and serotonin) had significant dominance variances (i.e., H(2) > h(2)). Surprisingly, there was little correlation between measures of heritability and the strength of association on a genomewide screen (P>.50), suggesting that heritability estimates per se do not identify phenotypes that are influenced by genes with major effects. The present study demonstrates the feasibility of genomewide association studies for QTL mapping. However, even in this young founder population that has extensive linkage disequilibrium, map densities <5 cM may be required to detect all major QTLs.     

Quantitative genetics of bioenergetics and growth-related traits in the wild mammal, Phyllotis darwini

We studied the potential for response to selection in typical physiological-thermoregulatory traits of mammals such as maximum metabolic rate (MMR), nonshivering thermogenesis (NST) and basal metabolic rate (BMR) on cold-acclimated animals. We used an animal model approach to estimate both narrow-sense heritabilities (h2) and genetic correlations between physiological and growth-related traits. Univariate analyses showed that MMR presented high, significant heritability (h2 = 0.69 +/- 0.35, asymptotic standard error), suggesting the potential for microevolution in this variable. However, NST and BMR presented low, nonsignificant h2, and NST showed large maternal/common environmental/nonadditive effects (c2 = 0.34 +/- 0.17). Heritabilities were large and significant (h2 > 0.5) for all growth-related traits (birth mass, growth rate, weaning mass). The only significant genetic correlations we found between a physiological trait and a growth-related trait was between NST and birth mass (r = -0.74; P < 0.05). Overall, these results suggest that additive genetic variance is present in several bioenergetic traits, and that genetic correlations could be present between those different kinds of traits.     

NATURAL HERITABILITIES: CAN THEY BE RELIABLY ESTIMATED IN THE LABORATORY?

The validity of the assumption, that laboratory estimates of heritabilities will tend to overestimate natural heritabilities, due to a reduction in environmental variability and thus the phenotypic variance of traits, is examined. One hundred sixty-five field estimates of narrow sense heritabilities derived from the literature are compared with 189 estimates from laboratory studies on wild, outbred animal populations derived from the data set of Mousseau and Roff. The results indicate that 84% of field heritabilities are significantly different from zero and that for morphological, behavioral, and life-history traits there are no significant differences between laboratory and field estimates of heritability. Unexpectedly, mean heritabilities for morphological and life-history traits are actually higher in the field than in the lab. Twenty-two cases were found for which both laboratory and natural heritabilities had been estimated on the same traits. For this subset of the data, laboratory heritabilities tended to be higher than field estimates, but the difference was not significant. Also, the correlation between lab and field estimates was high (r = 0.6, P < 0.001), and the regression slope did not differ significantly from one. The major implications of this study are that laboratory estimates of heritability should generally provide reasonable estimations of both the magnitude and the significance of heritabilities in nature.     

Estimating variance components and heritabilities in the wild: a case study using the ‘animal model’ approach

Using a genealogy containing over 1800 dams and nearly 400 sires (estimated by genetic paternity techniques), combined with maximum likelihood procedures and an ‘animal model’, we have estimated the heritabilities, genetic correlations and variance components of three morphometric traits in the Soay sheep (Ovis aries) on St Kilda, Scotland. This approach allows heritabilities to be estimated in natural populations that violate the assumptions of offspring–parent regression methods. Maternal (or paternal) effects can also be estimated under natural conditions. We demonstrate that all the traits, body weight, hind leg length and incisor arcade breadth, have low but significant heritabilities. Body weight, the trait that experiences the strongest selection, had the lowest heritability but the highest additive genetic coefficient of variation. An evolutionary response to selection is predicted. When maternal effects were not taken into consideration heritabilities were over‐estimated, although this effect was only significant in female offspring.     

Fasting insulin reflects heterogeneous physiological processes: role of insulin clearance

Several processes contribute to variation in fasting insulin concentration, including fasting glucose, insulin resistance, insulin secretion, and insulin clearance. Our goal was to determine the relative contribution of each of these insulin-related traits, plus anthropometric parameters, to fasting insulin among 470 Mexican Americans. The euglycemic hyperinsulinemic clamp yielded insulin sensitivity (M value) and metabolic clearance rate of insulin (MCRI). Acute insulin secretion was estimated by the insulinogenic index (IGI30) from the oral glucose tolerance test. Regression (univariate) and generalized estimating equations (multivariate) were used to describe the relationship of insulin-related traits to fasting insulin. Univarate analyses were used to select which traits to include in the multivariate model. In multivariate analysis, MCRI, M, BMI, waist circumference, and fasting glucose were independently associated with fasting insulin. Decreasing M and MCRI were associated with increasing fasting insulin, whereas increasing BMI, waist circumference, and fasting glucose were associated with increasing fasting insulin. Standardized coefficients allowed determination of the relative strength of each trait's association with fasting insulin in the entire cohort (strongest to weakest): MCRI (-0.35, P < 0.0001), M (-0.24, P < 0.0001), BMI (0.20, P = 0.0011), waist circumference (0.16, P = 0.021), and fasting glucose (0.11, P = 0.014). Fasting insulin is a complex phenotype influenced by several independent processes, each of which might have its own environmental and genetic determinants. One of the most associated traits was insulin clearance, which has implications for studies that have used fasting insulin as a surrogate for insulin resistance.     

The quantitative genetics of sexually selected traits,preferred traits and preference: a review and analysis of the data

The maintenance of variation in sexually selected traits is a puzzle that has received increasing attention in the past several decades. Traits that are related to fitness, such as life‐history or sexually selected traits, are expected to have low additive genetic variance (and hence, heritability) due to the rapid fixation of advantageous alleles. However, previous analyses have suggested that the heritabilities of sexually selected traits are on average higher than nonsexually selected traits. We show that the heritabilities of sexually selected traits are not significantly different from those of nonsexually selected traits overall or when separated into the three trait categories: behavioural, morphological and physiological. In contrast with previous findings, the heritability of preference is quite low (h² = 0.25 ± 0.06) and is in the same range as life‐history traits. We distinguish preferred traits as a category of sexually selected traits and find that the heritability of the former is not significantly different than sexually selected traits overall (0.48 ± 0.04 vs. 0.46 ± 0.03). We test the hypothesis that the heritability of sexually selected traits is negatively correlated with the strength of sexual selection. As predicted, there is a significant negative correlation between the heritabilities of sexually selected traits and the strength of selection. This suggests that heritabilities do indeed decrease as sexual selection increases but sexual selection is not strong enough to cause heritabilities of sexually selected traits to deviate from the same type of nonsexually selected traits.     

Evidence for higher heritability of somatotype compared to body mass index in female twins

The influence of genetics on human physique and obesity has been addressed by the literature. Evidence for heritability of anthropometric characteristics has been previously described, mainly for the body mass index (BMI). However, few studies have investigated the influence of genetics on the Heath-Carter somatotype. The aim of the present study was to assess the heritability of BMI and somatotype (endomorphy, mesomorphy, and ectomorphy) in a group of female monozygotic and dizygotic twins from childhood to early adulthood. A total of 28 females aged from 7 to 19 years old were studied. The group included 5 monozygotic and 9 dizygotic pairs of twins. The heritability was assessed by the twin method (h(2)). The anthropometric measures and somatotype were assessed using standard validated procedures. Significant differences between monozygotic and dizygotic pairs of twins were found for height, endomorphy, ectomorphy, and mesomorphy, and the heritability for these measures was high (h(2) between 0.88 and 0.97). No significant differences were found between monozygotic and dizygotic twins for weight, and the BMI and the heritability indexes were lower for these measures (respectively 0.42 and 0.52). The results of the present study have indicated that the somatotype may be more sensible to genetic influences than the BMI in females.     

Heritability variations of body linearity and obesity indicators during growth

Longitudinal as well as cross-sectional studies have shown variations with age in heritability estimates for body dimensions from infancy to adulthood, even though the patterns of variation are not completely clear. Further study on this subject is of great interest and may help obesity interventions for preventing or treating obesity in children. Therefore, the aim of the present study is to analyse the changes in the genetic and environmental architecture of 8 body linearity and obesity-related phenotypes during the growth process in a cross-sectional sample of 1018 nuclear families from the province of Biscay (Basque Country, Spain). The contribution of additive genetic effects to the variation of the analysed traits was estimated by a variance component analysis using the SOLAR program. Moderate to high heritability estimates were obtained for all 8 anthropometric phenotypes (38.23–65.98%). The heritability values show an increasing trend with age and in the course of the entire ontogenetic development two age periods were remarkable. At 7⁺–8⁺ years of age a strong increase in heritability estimates was found for all the anthropometric phenotypes, except for the sum of skinfolds (SF6), reflecting the biological significance of genes during mid-childhood. During puberty, most of the obesity related phenotypes showed their highest heritability values while linear measurements and weight presented a decrease in the genetic contributions. In conclusion, this study confirms that additive genetic influences have a considerable effect on body linearity and obesity-related traits throughout the growth period and that mid-childhood and puberty are very sensitive periods in human life cycle.     

Quantitative genetic variation of metabolism in the nymphs of the sand cricket, Gryllus firmus, inferred from an analysis of inbred-lines

Compared with morphological and life history traits, quantitative genetic variation of metabolic and related traits in animals has been poorly studied. We used flow-through VCO(2) respirometry and simultaneous activity measurement on nymphs of the sand cricket (Gryllus firmus) from inbred lines to estimate broad-sense heritability of four metabolic variables. In addition, we measured a number of linear dimensions in the adults from the same inbred lines. There were significant multivariate effects of inbred lines for all traits and broad-sense heritability for physiological traits was 4.5%, 5.2%, 10.3% and 8.5% for average, resting, minimum and maximum CO(2) production in nymphs, respectively. Though the MANOVA indicated significant genetic variation among inbred lines in adult morphology, the broad-sense heritabilities were relatively low ranging from 0-18%. Our results indicate that the heritabilities of metabolic measures are large enough to potentially respond to selection.     

Effects of Migration on Genetic Variability and Parent–Offspring Correlation Coefficients in Anthropometric and Physiometric Phenotypes Among Three Groups of Population in Punjab, India

In the present study, we examined the migration effects on genetic variabilities and heritabilities patterns between three groups of population like parental population in Punjab, migrant from Pakistan, and migrant from other states of India in Punjab using anthropometric and physiometric traits. A total of 500 adult individuals from 300 families were studied. Statistical comparisons were carried out through mean coefficients, Student’s t test, heritability, and regression analysis. The results suggest a significant migration effect on almost all traits. Correlation coefficient for first-degree relatives, the slope factors, and heritabilities for almost all variables have been found significant among the three groups of populations. However, the discrimination is more prominent among migrant from other states of India because of more genetic heterogeneity.     

Broad and narrow heritabilities of quantitative traits in a founder population

Estimation of the components of variance for a quantitative trait allows one to evaluate both the degree to which genetics influences the trait and the trait's underlying genetic architecture. For particular traits, the estimates also may have implications for discriminating between potential models of selection and for choosing an appropriate model for linkage analysis. Using a recently developed method, we estimate the additive and dominance components of variance--or, equivalently, the narrow and broad sense heritabilities--of several traits in the Hutterites, a founder population with extensive genealogical records. As a result of inbreeding and because Hutterite individuals are typically related through multiple lines of descent, we expect that power to detect dominance variance will be increased relative to that in outbred studies. Furthermore, the communal lifestyle of the Hutterites allows us to evaluate the genetic influences in a relatively homogeneous environment. Four phenotypes had a significant dominance variance, resulting in a relatively high broad heritability. We estimated the narrow and broad heritabilities as being, respectively,.36 and.96 for LDL,.51 and 1.0 for serotonin levels, and.45 and.76 for fat free mass (FFM). There was no significant additive component for systolic blood pressure (SBP), resulting in a narrow heritability of 0 and a broad heritability of.45. There were several traits for which we found no significant dominance component, resulting in equal broad and narrow heritability estimates. These traits and their heritabilities are as follows: HDL,.63; triglycerides,.37; diastolic blood pressure,.21; immunoglobulin E,.63; lipoprotein(a),.77; and body-mass index,.54. The large difference between broad and narrow heritabilities for LDL, serotonin, FFM, and SBP are indicative of strong dominance effects in these phenotypes. To our knowledge, this is the first study to report an estimate of heritability for serotonin and to detect a dominance variance for LDL, FFM, and SBP.     

A genetic contribution to circulating cytokines and obesity in children

Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children enrolled in VIVA LA FAMILIA Study. Cytokine phenotypes included monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta 1 (TGF-beta1), C-reactive protein (CRP), regulated upon activation, normal T-cell expressed and secreted (RANTES) and eotaxin. Obesity-related phenotypes included body mass index (BMI), fat mass (FM), truncal FM and fasting serum insulin. Heritabilities ranged from 0.33 to 0.97. Pleiotropy was observed between cytokines and obesity traits. Positive genetic correlations were seen between CRP, leptin, MCP-1 and obesity traits, and negative genetic correlations with adiponectin, ICAM-1 and TGF-beta1. Genome-wide scan of sICAM-1 mapped to chromosome 3 (LOD=3.74) between markers D3S1580 and D3S1601, which flanks the adiponectin gene (ADIPOQ). Suggestive linkage signals were found in other chromosomal regions for other cytokines. In summary, significant heritabilities for circulating cytokines, pleiotropy between cytokines and obesity traits, and linkage for sICAM-1 on chromosome 3q substantiate a genetic contribution to circulating cytokine levels in Hispanic children.