Body Adiposity Index versus Body Mass Index and Other Anthropometric Traits as Correlates of Cardiometabolic Risk Factors

Objective

The worldwide prevalence of obesity mandates a widely accessible tool to categorize adiposity that can best predict associated health risks. The body adiposity index (BAI) was designed as a single equation to predict body adiposity in pooled analysis of both genders. We compared body adiposity index (BAI), body mass index (BMI), and other anthropometric measures, including percent body fat (PBF), in their correlations with cardiometabolic risk factors. We also compared BAI with BMI to determine which index is a better predictor of PBF.

Methods

The cohort consisted of 698 Mexican Americans. We calculated correlations of BAI, BMI, and other anthropometric measurements (PBF measured by dual energy X-ray absorptiometry, waist and hip circumference, height, weight) with glucose homeostasis indices (including insulin sensitivity and insulin clearance from euglycemic clamp), lipid parameters, cardiovascular traits (including carotid intima-media thickness), and biomarkers (C-reactive protein, plasminogen activator inhibitor-1 and adiponectin). Correlations between each anthropometric measure and cardiometabolic trait were compared in both sex-pooled and sex-stratified groups.

Results

BMI was associated with all but two measured traits (carotid intima-media thickness and fasting glucose in men), while BAI lacked association with several variables. BAI did not outperform BMI in its associations with any cardiometabolic trait. BAI was correlated more strongly than BMI with PBF in sex-pooled analyses (r = 0.78 versus r = 0.51), but not in sex-stratified analyses (men, r = 0.63 versus r = 0.79; women, r = 0.69 versus r = 0.77). Additionally, PBF showed fewer correlations with cardiometabolic risk factors than BMI. Weight was more strongly correlated than hip with many of the cardiometabolic risk factors examined.

Conclusions

BAI is inferior to the widely used BMI as a correlate of the cardiometabolic risk factors studied. Additionally, BMI’s relationship with total adiposity may not be the sole determinate of its association with cardiometabolic risk.     

Genetic Variability of Adult Body Mass Index: A Longitudinal Assessment in Framingham Families

Objective: To explore the contribution of genetics to the mean, SD, maximum value, maximum less the mean, and change over time in body mass index (BMI) and the residual of body weight after adjustment for height. BMI is frequently used as a general indicator of obesity because of its ease and reliability in ascertainment. Cross‐sectional twin and family studies have shown a moderate‐to‐substantial genetic component for BMI. However, the contribution of genetics to the long‐term average, variability, or change over time in BMI is less clear. Research Methods and Procedures: Longitudinal data from the Framingham heart study were used to create pedigrees of age‐matched individuals. Heritability estimates were derived using variance‐decomposition methods on a total of 1051 individuals from 380 extended pedigrees followed for a period of 20 years. All subjects were followed from approximately age 35 to 55 years. Results: Moderate heritability estimates were found for the mean BMI (h² = 0.37), maximum BMI (h² = 0.40), and the mean residual of body weight (h² = 0.36). Low heritability estimates (h² ? 0.20) were found for the maximum less the mean in BMI and the SDs of BMI and residual of body weight. No additive genetic contribution was found for the average change over time in BMI or the residual of body weight. Discussion: These findings suggest that there is a significant genetic component for the magnitude of BMI throughout an individual's middle‐adult years; however, little evidence was found for a genetic contribution to the variability or rate of change in an individual's BMI.     

Genome-Wide Association Study of Lp-PLA2 Activity and Mass in the Framingham Heart Study

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is an emerging risk factor and therapeutic target for cardiovascular disease. The activity and mass of this enzyme are heritable traits, but major genetic determinants have not been explored in a systematic, genome-wide fashion. We carried out a genome-wide association study of Lp-PLA₂ activity and mass in 6,668 Caucasian subjects from the population-based Framingham Heart Study. Clinical data and genotypes from the Affymetrix 550K SNP array were obtained from the open-access Framingham SHARe project. Each polymorphism that passed quality control was tested for associations with Lp-PLA₂ activity and mass using linear mixed models implemented in the R statistical package, accounting for familial correlations, and controlling for age, sex, smoking, lipid-lowering-medication use, and cohort. For Lp-PLA₂ activity, polymorphisms at four independent loci reached genome-wide significance, including the APOE/APOC1 region on chromosome 19 (p = 6×10⁻²⁴); CELSR2/PSRC1 on chromosome 1 (p = 3×10⁻¹⁵); SCARB1 on chromosome 12 (p = 1×10⁻⁸) and ZNF259/BUD13 in the APOA5/APOA1 gene region on chromosome 11 (p = 4×10⁻⁸). All of these remained significant after accounting for associations with LDL cholesterol, HDL cholesterol, or triglycerides. For Lp-PLA₂ mass, 12 SNPs achieved genome-wide significance, all clustering in a region on chromosome 6p12.3 near the PLA2G7 gene. Our analyses demonstrate that genetic polymorphisms may contribute to inter-individual variation in Lp-PLA₂ activity and mass.     

Genome-Wide Association Studies and Heritability Estimates of Body Mass Index Related Phenotypes in Bangladeshi Adults

Many health outcomes are influenced by a person''s body mass index, as well as by the trajectory of body mass index through a lifetime. Although previous research has established that body mass index related traits are influenced by genetics, the relationship between these traits and genetics has not been well characterized in people of South Asian ancestry. To begin to characterize this relationship, we analyzed the association between common genetic variation and five phenotypes related to body mass index in a population-based sample of 5,354 Bangladeshi adults. We discovered a significant association between SNV rs347313 (intron of NOS1AP) and change in body mass index in women over two years. In a linear mixed-model, the G allele was associated with an increase of 0.25 kg/m² in body mass index over two years (p-value of 2.3·10⁻⁸). We also estimated the heritability of these phenotypes from our genotype data. We found significant estimates of heritability for all of the body mass index-related phenotypes. Our study evaluated the genetic determinants of body mass index related phenotypes for the first time in South Asians. The results suggest that these phenotypes are heritable and some of this heritability is driven by variation that differs from those previously reported. We also provide evidence that the genetic etiology of body mass index related traits may differ by ancestry, sex, and environment, and consequently that these factors should be considered when assessing the genetic determinants of the risk of body mass index-related disease.     

Methylation Profiles Reveal Distinct Subgroup of Hepatocellular Carcinoma Patients with Poor Prognosis

Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-associated mortality worldwide. However, the role of epigenetic changes such as aberrant DNA methylation in hepatocarcinogenesis remains largely unclear. In this study, we examined the methylation profiles of 59 HCC patients. Using consensus hierarchical clustering with feature selection, we identified three tumor subgroups based on their methylation profiles and correlated these subgroups with clinicopathological parameters. Interestingly, one tumor subgroup is different from the other 2 subgroups and the methylation profile of this subgroup is the most distinctly different from the non-tumorous liver tissues. Significantly, this subgroup of patients was found to be associated with poor overall as well as disease-free survival. To further understand the pathways modulated by the deregulation of methylation in HCC patients, we integrated data from both the methylation as well as the gene expression profiles of these 59 HCC patients. In these patients, while 4416 CpG sites were differentially methylated between the tumors compared to the adjacent non-tumorous tissues, only 536 of these CpG sites were associated with differences in the expression of their associated genes. Pathway analysis revealed that forty-four percent of the most significant upstream regulators of these 536 genes were involved in inflammation-related NFκB pathway. These data suggest that inflammation via the NFκB pathway play an important role in modulating gene expression of HCC patients through methylation. Overall, our analysis provides an understanding on aberrant methylation profile in HCC patients.     

Integration-independent Transgenic Huntington Disease Fragment Mouse Models Reveal Distinct Phenotypes and Life Span in Vivo

The cascade of events that lead to cognitive decline, motor deficits, and psychiatric symptoms in patients with Huntington disease (HD) is triggered by a polyglutamine expansion in the N-terminal region of the huntingtin (HTT) protein. A significant mechanism in HD is the generation of mutant HTT fragments, which are generally more toxic than the full-length HTT. The protein fragments observed in human HD tissue and mouse models of HD are formed by proteolysis or aberrant splicing of HTT. To systematically investigate the relative contribution of the various HTT protein proteolysis events observed in vivo, we generated transgenic mouse models of HD representing five distinct proteolysis fragments ending at amino acids 171, 463, 536, 552, and 586 with a polyglutamine length of 148. All lines contain a single integration at the ROSA26 locus, with expression of the fragments driven by the chicken β-actin promoter at nearly identical levels. The transgenic mice N171-Q148 and N552-Q148 display significantly accelerated phenotypes and a shortened life span when compared with N463-Q148, N536-Q148, and N586-Q148 transgenic mice. We hypothesized that the accelerated phenotype was due to altered HTT protein interactions/complexes that accumulate with age. We found evidence for altered HTT complexes in caspase-2 fragment transgenic mice (N552-Q148) and a stronger interaction with the endogenous HTT protein. These findings correlate with an altered HTT molecular complex and distinct proteins in the HTT interactome set identified by mass spectrometry. In particular, we identified HSP90AA1 (HSP86) as a potential modulator of the distinct neurotoxicity of the caspase-2 fragment mice (N552-Q148) when compared with the caspase-6 transgenic mice (N586-Q148).     

Evidence for Multiple Determinants of the Body Mass Index: The National Heart,Lung, and Blood Institute Family Heart Study

The body mass index (BMI) is a complex phenotype representing the amount of fat mass, lean mass, body build and proportions, and it is likely to be affected by various metabolic processes, hormonal effects, energy intake and expenditure, and interactions within and among these broad categories of etiologic factors. Nonetheless, several previous studies have reported evidence for major gene segregation for the BMI in various populations. Data on a random sample of Caucasian families participating in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study were analyzed to document the extent of familial resemblance and to investigate whether a similar monogenic inheritance pattern could be detected. Genetic analysis was carried out on age- and sex-adjusted BMI values. Familial correlations were significant implying a maximal heritability, including all genetic and environmentally inherited additive factors, of 41% to 59%. Segregation analysis revealed the presence of two maximum likelihood solutions, one characterized as a recessive Mendelian gene and the other as a major effect with an ambiguous transmission pattern. The presence of two such solutions is consistent with detection of two separate factors, each influencing the BMI distribution in a substantive manner. The evidence also supports a multifactorial background for BMI and suggests that the frequencies of these two factors, one of which appears to be a gene, may vary among diverse populations in the United States.     

Relationships Between the Body Mass Index and Body Composition

The aims of this study were to evaluate the Body Mass Index (BMI) (weight/stature²) as a proxy for percent body fat (%BF) and to determine its association with fat-free mass (FFM). Multivariate analysis of variance and partial correlations were used to examine relationships between BMI and %BF and FFM from densitometry for 504 men and 511 women, aged 20 to 45 years. Sensitivity/specificity analyses used cut offs of 28 kg/m² in men and 26 kg/m² in women for BMI, and 25% in men and 33% in women for %BF. Significantly higher associations existed in each gender between BMI and %BF in the upper BMI tertile than in the lower BMI tertiles. In the lower BMI tertiles, correlations between BMI and FFM were approximately twice as large as those between BMI and %BF. The BMI correctly identified about 44% of obese men, and 52% of obese women when obesity was determined from %BF. BMI is an uncertain diagnostic index of obesity. Results of Receiver Operator Characteristic (ROC) analyses using %BF and total body fat, both provided a BMI of 25 kg/m² in men and 23 kg/m² in women as diagnostic screening cut offs for obesity.     

体重指数在评估内科住院患者肺心病发生中的价值

目的：探讨体重指数在预测内科住院患者肺心病发生中的价值。方法：利用随机数表随机入选解放军第十二医院2012年1月～2012年12月间内科住院患者92例,其中男性47例,女性45例,年龄在22岁-87岁之间。体重指数（Bodymassindex,BMI）应用公式：BMI=体重／身高。（kg／m2）计算。用酶法检测血清总胆固醇、甘油三酯;葡萄糖氧化酶法测定空腹血糖。结果：与非肺心病组患者比较,肺心病组患者体重指数明显升高（38．96±5．77VS29．72±7．879,P〈0．01）;肺心病组患者肺性脑病病史的比率明显升高（26．7％VSO％,P〈0．01）。肥胖和极度肥胖的患者合并肺心病病史的比率分别为53．3％、46．7％。多分类Logistic回归分析显示,体重指数与肺心病密切相关。ROC曲线分析显示,体重指数预测肺心病的临界值为BMI〉32kg／m2,预测肺心病的ROC曲线下面积为0．860,ROC曲线下面积大于0．7,预测价值较高。Youden指数为0．596,体重指数预测最佳临界值为BMI大于32,诊断特异性为66．2％,敏感性为93．3％,阳性预测值为34．96％,阴性预测值为98．07％。结论：内科住院患者体重指数与肺心病发病率密切相关,体重指数大于32kg／m。预测内科住院患者肺心病发病有较高的价值。     

体重指数在评估内科住院患者肺心病发生中的价值

目的:探讨体重指数在预测内科住院患者肺心病发生中的价值。方法:利用随机数表随机入选解放军第十二医院2012年1月~2012年12月间内科住院患者92例,其中男性47例,女性45例,年龄在22岁~87岁之间。体重指数(Body mass index,BMI)应用公式:BMI=体重/身高2(kg/m2)计算。用酶法检测血清总胆固醇、甘油三酯;葡萄糖氧化酶法测定空腹血糖。结果:与非肺心病组患者比较,肺心病组患者体重指数明显升高(38.96±5.77 vs 29.72±7.879,P0.01);肺心病组患者肺性脑病病史的比率明显升高(26.7%vs 0%,P0.01)。肥胖和极度肥胖的患者合并肺心病病史的比率分别为53.3%、46.7%。多分类Logistic回归分析显示,体重指数与肺心病密切相关。ROC曲线分析显示,体重指数预测肺心病的临界值为BMI32 kg/m2,预测肺心病的ROC曲线下面积为0.860,ROC曲线下面积大于0.7,预测价值较高。Youden指数为0.596,体重指数预测最佳临界值为BMI大于32,诊断特异性为66.2%,敏感性为93.3%,阳性预测值为34.96%,阴性预测值为98.07%。结论:内科住院患者体重指数与肺心病发病率密切相关,体重指数大于32 kg/m2预测内科住院患者肺心病发病有较高的价值。     

Pedigree and genotype errors in the Framingham Heart Study

The pedigree and genotype data from the Framingham Heart Study were examined for errors. Errors in 21 of 329 pedigrees were detected with the program PREST, and of these the errors in 16 pedigrees were resolved. Genotyping errors were then detected with SIMWALK2. Five Mendelian errors were found following the pedigree corrections. Double-recombinant errors were more common, with 142 being detected at mistyping probabilities of 0.25 or greater.     

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.     

体重指数与支气管哮喘的相关性研究

目的：探讨体重指数（BMI）对支气管哮喘的影响,进一步揭示肥胖与哮喘在肺功能方面的内在联系,从而对哮喘的防治提供新的研究方向。方法：选取我院肺功能室2009年3月至2011年1月支气管哮喘患者97例,其中男性51例,女性46例,年龄20-42岁,依据体重指数分级,分为正常体重组35例,超重组32例,肥胖组30例。进行肺功能及支气管舒张试验测定,分组比较。结果：（1）超重组和肥胖组改善率高于正常体重组（P=0.012,P=0.002）。（2）FVC和FEV1/FVC在哮喘患者中下降明显（P〈0.05）,有显著差异。结论：（1）体重指数影响哮喘改善率,随体重指数的增加改善率也相应增加（2）肥胖哮喘患者仍以阻塞性通气功能障碍为主。     

Longitudinal variance-components analysis of the Framingham Heart Study data

The Framingham Heart Study offspring cohort, a complex data set with irregularly spaced longitudinal phenotype data, was made available as part of Genetic Analysis Workshop 13. To allow an analysis of all of the data simultaneously, a mixed-model- based random-regression (RR) approach was used. The RR accounted for the variation in genetic effects (including marker-specific quantitative trait locus (QTL) effects) across time by fitting polynomials of age. The use of a mixed model allowed both fixed (such as sex) and random (such as familial environment) effects to be accounted for appropriately. Using this method we performed a QTL analysis of all of the available adult phenotype data (26,106 phenotypic records). In addition to RR, conventional univariate variance component techniques were applied. The traits of interest were BMI, HDLC, total cholesterol, and height. The longitudinal method allowed the characterization of the change in QTL effects with aging. A QTL affecting BMI was shown to act mainly at early ages.