Comparisons between dual-energy X-ray absorptiometry and bioimpedance devices for appendicular lean mass and muscle quality in Hispanic adults.

The purpose of this study was to compare single- and multi-frequency bioimpedance (BIA) devices against dual-energy X-ray absorptiometry (DXA) for appendicular lean mass (ALM) and muscle quality index (MQI) metrics in Hispanic adults. One hundred thirty-one Hispanic adults (18-55 years) participated in this study. ALM was measured with single-frequency bioimpedance analysis (SFBIA), multi-frequency bioimpedance analysis (MFBIA) and DXA. ALMTOTAL (left arm + right arm + left leg + right leg) and ALMARMS (left arm + right arm) were computed for all three devices. Handgrip strength (HGS) was measured using a dynamometer. The average HGS was used for all MQI models (highest left hand + highest right hand)/2. MQIARMS was defined as the ratio between HGS and ALMARMS. MQITOTAL was established as the ratio between HGS and ALMTOTAL. SFBIA and MFBIA had strong correlations with DXA for all ALM and MQI metrics (Lin's concordance correlation coefficient values ranged from 0·86 (MQIMFBIA-ARMS) to 0·97 (Arms LMSFBIA); all P < 0·001). Equivalence testing varied between methods (e.g. SFBIA v. DXA) when examining the different metrics (i.e. ALMTOTAL, ALMARMS, MQITOTAL and MQIARMS). MQIARMS was the only metric that did not differ from the line of identity and had no proportional bias when comparing all the devices against each other. The current study findings demonstrate good overall agreement between SFBIA, MFBIA and DXA for ALMTOTAL and ALMARMS in a Hispanic population. However, SFBIA and MFBIA have better agreement with DXA when used to compute MQIARMS than MQITOTAL.

Genetic correlations between liver fat content, metabolic health, and adiposity distribution in the Fels Longitudinal Study.

BACKGROUND AND AIMS: Hepatic steatosis is known to be heritable, but its genetic basis is mostly uncharacterized. Steatosis is associated with metabolic and adiposity features; recent studies hypothesize that shared genetic effects between these traits could account for some of the unexplained heritability. This study aimed to quantify these genetic associations in a family-based sample of non-Hispanic white adults. METHODS AND RESULTS: 704 participants (18-95 years, 55.8% female) from the Fels Longitudinal Study with an MRI assessment of liver fat were included. Quantitative genetic analyses estimated the age- and sex-adjusted heritability of individual traits and the genetic correlations within trait pairs. Mean liver fat was 5.95% (SE = 0.23) and steatosis (liver fat >5.56%) was present in 29.8% of participants. Heritability (h2± SE) of steatosis was 0.72 ± 0.17 (p = 6.80e-6). All other traits including liver enzymes, fasting glucose, HOMA-IR, visceral and subcutaneous adipose tissue (VAT, SAT), body mass index, body fat percent, waist circumference, lipids and blood pressure were also heritable. Significant genetic correlations were found between liver fat and all traits except aspartate aminotransferase (AST), and among most trait pairs. Highest genetic correlations were between liver fat and HOMA-IR (0.85 ± 0.08, p = 1.73e-8), fasting glucose and ALT (0.89 ± 0.26, p = 6.68e-5), and HOMA-IR with: waist circumference (0.81 ± 0.12, p = 3.76e-6), body fat percent (0.78 ± 0.12 p = 2.42e-5) and VAT (0.73 ± 0.07, p = 6.37e-8). CONCLUSIONS: Common genes may exist between liver fat accumulation, metabolic features and adiposity phenotypes.

Anti-Müllerian hormone levels are associated with skeletal maturity in adolescent girls in the Fels Longitudinal Study.

The role of anti-Müllerian hormone (AMH), a potential marker of the hypothalamic-pituitary-ovarian axis, is not well established in adolescent females. Most studies use secondary sexual characteristics or chronological age as predictors for AMH. Skeletal maturity, an indicator of bone development, has not been examined to predict AMH. This study sought to examine patterns of change in AMH in relation to skeletal maturity. Demographics, anthropometry, hand-wrist radiographs, and cardiometabolic risk factors from 88 females (212 observations), between the ages of 8 to 18 years from the Fels Longitudinal Study were used in this study. AMH was analyzed using ELISA from stored frozen serum samples. Generalized linear mixed effect modeling was used. In the stepwise regression models, log-transformed AMH (AMHlog) was regressed on relative skeletal age as the skeletal maturity indicator (calculated as chronological age minus skeletal age) and adjusted for chronological age, adiposity, and cardiometabolic risk factors. Skeletal maturity significantly predicted lower AMHlog (ß= -0.073, SE=0.032, p=0.023). Glucose was significantly associated with decreases in AMHlog (ß= -0.008, SE=0.004, p=0.044). Chronological age modeled as a cubic function was not significant. AMH and skeletal maturity may provide correlated information on growth and pubertal status in adolescent females.

Deuterium oxide validation of bioimpedance total body water estimates in Hispanic adults.

Background: To date, body composition assessments in Hispanics, computed via bioimpedance devices, have primarily focused on body fat percent, fat mass, and fat-free mass instead of total body water (TBW). Additionally, virtually no information is available on which type of bioimpedance device is preferred for TBW assessments in Hispanic populations. Purpose: The purpose of this study was to validate two bioimpedance devices for the estimate of TBW in Hispanics adults when using a criterion deuterium oxide (D2O) technique. Methods: One-hundred thirty individuals (males: n = 70; females: n = 60) of Hispanic descent had TBW estimated via D2O, single-frequency bioimpedance analysis ([SF-BIA] Quantum V, RJL Systems) and bioimpedance spectroscopy ([BIS] SFB7 Impedimed). Results: The mean values for SF-BIA were significantly lower than D2O when evaluating the entire sample (37.4 L and 38.2 L, respectively; p < 0.05). In contrast, TBW values were not statistically significant when comparing D2O against BIS (38.4 L, p > 0.05). Bland-Altman analysis indicated no proportional bias when evaluating the entire sample for SF-BIA or BIS. The standard error of estimate and total error values were ≤ 2.3 L and Lin's concordance correlation coefficient were ≥ 0.96 for all comparisons. Conclusion: The SF-BIA and BIS devices evaluated in the current study hold promise for accurate estimation of TBW in Hispanic adults. While both methods demonstrated relatively low errors relative to the D2O criterion, BIS exhibited a more consistent performance, particularly at the group level. These findings provide essential information for researchers and clinical nutrition practitioners assessing TBW in Hispanic adults.

Evaluation of a Rapid Four-Compartment Model and Stand-Alone Methods in Hispanic Adults.

BACKGROUND: A rapid 4-compartment (4C) model integrates dual-energy x-ray absorptiometry (DXA) and multi-frequency bioimpedance analysis (MFBIA), which may be useful for clinical and research settings seeking to employ a multi-compartment model. OBJECTIVES: This study aimed to determine the added benefit of a rapid 4C model over stand-alone DXA and MFBIA when estimating body composition. METHODS: One hundred and thirty participants (n = 60 male; n = 70 female) of Hispanic descent were included in the present analysis. A criterion 4C model that employed air displacement plethysmography (body volume), deuterium oxide (total body water), and DXA (bone mineral) was used to measure fat mass (FM), fat-free mass (FFM), and body fat percent (%BF). A rapid 4C model (DXA-derived body volume and bone mineral; MFBIA-derived total body water) and stand-alone DXA (GE Lunar Prodigy) and MFBIA (InBody 570) assessments were compared against the criterion 4C model. RESULTS: Lin's concordance correlation coefficient values were >0.90 for all comparisons. The standard error of the estimates ranged from 1.3 to 2.0 kg, 1.6 to 2.2 kg, and 2.1 to 2.7% for FM, FFM, and %BF, respectively. The 95% limits of agreement ranged from ±3.0 to 4.2 kg, ±3.1 to 4.2 kg, and ±4.9 to 5.2% for FM, FFM, and %BF, respectively. CONCLUSIONS: Results revealed that all 3 methods provided acceptable body composition results. The MFBIA device used in the current study may be a more economically friendly option than DXA or when there is a need to minimize radiation exposure. Nonetheless, clinics and laboratories that already have a DXA device in place or that value having the lowest individual error when conducting a test may consider continuing to use the machine. Lastly, a rapid 4C model may be useful for assessing body composition measures observed in the current study and those provided by a multi-compartment model (e.g., protein).

Perceived quality of sleep across the menopausal transition: A retrospective cohort study.

Background and Aims: To compare sleep quality among naturally and surgically post-menopausal women, and to identify lifestyle factors that predict sleep quality in pre, peri, and postmenopausal women. Methods: This is a retrospective cohort study of data collected from 429 women who participated in Fels Longitudinal Study data. Sleep quality, based on the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, demographics, medical history, depression, quality of life, and physical activity levels were included in the analysis. Results: The four study groups did not differ on overall sleep quality with either scale (p = 0.61). Both Post-M groups were more likely to have a major sleep problem than the Peri-M and Pre-M groups (p < 0.001), and to have a history of restless leg syndrome (p = 0.016), but the two Post-M groups did not differ on these problems. Predictors of sleep quality included depression, bodily pain, vitality, and surgical menopause (p<0.001). Conclusion: Menopause is associated with sleep disrupting conditions. This study did not find any significant differences in sleep quality among the three reproductive stages or for natural versus surgical menopause. Women may benefit from addressing other lifestyle factors associated with poor sleep quality including mental health factors.

Effect of total body water estimates via bioimpedance on bod pod-based three-compartment body fat models.

BACKGROUND/OBJECTIVES: Previous research has compared 2- and 3-compartment (2C and 3C, respectively) models against criterion 4-compartment (4C) models while utilizing the same body density (Db) method for all measures. This design induces an inherent bias and obscures the added benefit of a 3C model over the simpler 2-compartment (2C) models. PURPOSE: The purpose of this study was to determine the effect of total body water estimates via single-frequency (SF-BIA) and multi-frequency (MF-BIA) bioimpedance analysis on body fat estimates derived from air displacement plethysmography (ADP)-derived 3C models. SUBJECTS/METHODS: A sample of 95 females and 82 males (n = 177) participated in this study. Underwater weighing, dual energy X-ray absorptiometry, and bioimpedance spectroscopy were used to calculate percent fat (%Fat) via a criterion 4C model (4CCRITERION). %Fat was predicted via 3CMFBIA (ADP and MF-BIA), 3CSFBIA (ADP and SF-BIA), and a stand-alone 2-compartment (2C) model, based upon ADP, when using Siri and Brozek body density conversion formulas (2CSIRI and 2CBROZEK. respectively). RESULTS: The standard error of estimate (SEE) was lowest for 3CSFBIA when evaluated in females and males (2.72% and 2.31%, respectively) and highest for 2CSIRI (3.98% and 3.84%, respectively). Similarly, the total error (TE) for females and males was lowest for 3CSFBIA (3.21% and 2.67%, respectively) and highest for 2CSIRI (4.58% and 4.48%, respectively) and 2CBROZEK (4.65% and 4.33%, respectively). CONCLUSIONS: Results suggest that SF-BIA and MF-BIA can improve the estimation of %Fat, beyond simpler 2C models, when integrated with ADP in a more advanced 3C model. Furthermore, the present study revealed that 3CSFBIA was the best overall prediction model based upon TE values. The current study results support the integration of ADP and bioimpedance technology as part of a 3C model for the improvement of %Fat estimates over simpler 2C models.

Longitudinal antimüllerian hormone and its correlation with pubertal milestones.

OBJECTIVE: To examine the changes in AMH levels longitudinally over time and their relationship with both body composition, particularly abdominal adiposity, and milestones of pubertal development in female children. DESIGN: Secondary analysis of a prospective, longitudinal study. SETTING: University affiliated research center and laboratories. PATIENTS: Eighty-nine females were examined between 1990 and 2015 to study child growth and development. INTERVENTIONS: Demographic, anthropometric, growth, and pubertal milestone data with serum samples stored and subsequently analyzed for AMH. MAIN OUTCOME MEASURES: Longitudinal change in AMH and predicted AMH levels based on body composition, age, and pubertal milestones including, pubarche, thelarche, and menarche. RESULTS: Natural log-transformed AMH (AMHlog) levels appeared to have a nonlinear relationship with age, decreasing between 10 and 14 years of age, increasing until 16 years. A mixed effect linear model demonstrated that increased abdominal adiposity (waist/height ratio, WHtR) was significantly associated with the predicted increased AMHlog levels (ß=1.37). As females progressed through the Tanner stages, the model predicted decreasing AMHlog values when adjusting for age and WHtR. CONCLUSIONS: Declining AMH levels during puberty may not be reflective of diminished ovarian reserve as observed in adults, but may suggest a permissive role of AMH in the activation of the hypothalamic-pituitary-ovarian axis.

The impact of metabolic syndrome on mental health-related quality of life and depressive symptoms.

PURPOSE: Results examining associations between metabolic syndrome (MetS) and depression, as well as on quality of life (QoL), are inconsistent. We aimed to determine whether individuals with MetS had decreased mental health-related QoL (MH-QoL) and higher frequency of depressive symptoms. METHODS: Data from 1,015 participants from the Fels Longitudinal Study were analyzed (mean age ± SD: 49.6 ± 18.7 years, 29.3% MetS, 51% females). MetS was determined using American Heart Association/National Heart, Lung, and Blood Institute criteria. Depressive symptoms (yes vs. no) were assessed with The Patient Health Questionnaire-9 (PHQ-9). MH-QoL (low (≤ 42) vs. high) was assessed with The Medical Outcomes 36-Item Short Form Survey (SF-36). Sex- and age-stratified mixed effects logistic regressions were used to examine the longitudinal relationship between MetS and MH-QoL while adjusting for covariates such as age, smoking status, and drinking status. RESULTS: In cross-sectional analysis, MetS was significantly associated with elevated depressive symptoms in women (OR 2.14, 95% CI 1.22-3.78, p < 0.01), but not in men. In the longitudinal analysis, MetS was observed to have a protective effect among men in the older age group as it approached significance (OR 0.34, 95% CI 0.11-1.05, p = 0.06). CONCLUSION: MetS was adversely associated with depressive symptoms and poor MH-QoL. Our cross-sectional results suggest that depressive symptoms are higher among women with MetS. Interestingly, our longitudinal results suggest that MH-QoL in men with MetS may improve with age.

Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry.

Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with ∼2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p ≤ 2.6 × 10-8 ) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 × 10-5 ). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. © 2019 American Society for Bone and Mineral Research.

Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10-8; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

Inverse associations between cardiometabolic risk factors and 25-hydroxyvitamin D in obese American children and adolescents.

OBJECTIVES: To examine the association between 25-hydroxyvitamin D [25(OH)D] concentrations and cardiometabolic risk factors in obese American children. METHODS: A cross-sectional study was conducted on 209 obese children (55% females, 25.8% black) aged between 6 and 19 years old. Study measurements included plasma 25(OH)D concentrations, blood pressure, lipids and oxidized LDL levels, insulin resistance (IR) indices from glucose, insulin and 5 hour oral glucose tolerance test. RESULTS: Fifty-one percent of the children had vitamin D deficiency. Older age [OR (95% CI) = 1.16 (1.00, 1.35)], black race/ethnicity [15.39 (5.79, 40.92)], winter/spring season [3.46 (1.69, 7.02)] and higher body mass index (BMI) [1.05 (0.99, 1.11)] were associated with increased odds of having vitamin D deficiency. None of cardiometabolic risk factors examined were significantly associated with vitamin D deficiency in age, race/ethnicity, season, and BMI adjusted models. In age, race/ethnicity, season and BMI adjusted models, total cholesterol (ß = -0.001, P = 0.013), non-HDL-C (ß = -0.001, P = 0.014), and oxidized LDL (ß = -0.087, P = 0.045) were inversely associated with log-transformed 25(OH)D. An approximate 10 mg/dl increase in total cholesterol or in non-HDL-C was associated with an approximate 1.3% decrease in the geometric mean of 25(OH)D concentration. Further a 10% increase in ox-LDL levels was associated with an approximate 0.8% decrease in the geometric mean of 25(OH)D. CONCLUSION: Vitamin D deficiency is prevalent in obese American children. There was evidence that some cardiometabolic risk factors including lipid levels and oxidized LDL levels were significantly inversely associated with 25(OH)D concentration in our sample. Am. J. Hum. Biol. 28:736-742, 2016. © 2016 Wiley Periodicals, Inc.

Validation of Maturity Offset in the Fels Longitudinal Study.

Sex-specific equations for predicting maturity offset, time before or after peak height velocity (PHV), were evaluated in 63 girls and 74 boys from the Fels Longitudinal Study. Serially measured heights (0.1 cm), sitting heights (0.1 cm), weights (0.1 kg), and estimated leg lengths (0.1 cm) from 8 to 18 years were used. Predicted age at PHV (years) was calculated as the difference between chronological age (CA) and maturity offset. Actual age at PHV for each child was derived with a triple logistic model (Bock-Thissen-du Toit). Mean predicted maturity offset was negative and lowest at 8 years and increased linearly with increasing CA. Predicted ages at PHV increased linearly with CA from 8 to 18 years in girls and from 8 to 13 years in boys; predictions varied within relatively narrow limits from 12 to 15 years and then increased to 18 years in boys. Differences between predicted and actual ages at PHV among youth of contrasting maturity status were significant across the age range in both sexes. Dependence of predicted age at PHV upon CA at prediction and on actual age at PHV limits its utility as an indicator of maturity timing and in sport talent programs.

Association of Perfluoroalkyl Substances, Bone Mineral Density, and Osteoporosis in the U.S. Population in NHANES 2009-2010.

BACKGROUND: Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), are detectable in the serum of 95% of the U.S. OBJECTIVE: Considering the role of PFASs as endocrine disruptors, we examined their relationships with bone health. METHODS: The association between serum PFAS concentration and bone mineral density at total femur (TFBMD), femoral neck (FNBMD), lumbar spine (LSBMD), and physician-diagnosed osteoporosis was assessed in 1,914 participants using data from the National Health and Nutritional Examination Survey 2009-2010. RESULTS: The mean age of the participants was 43 years. Men had higher serum PFAS concentrations than women (p < 0.001) except for PFNA. In both sexes, serum PFOS concentrations were inversely associated with FNBMD (p < 0.05). In women, significant negative associations were observed for natural log (ln)-transformed PFOS exposure with TFBMD and FNBMD, and for ln-transformed PFOA exposure with TFBMD (p < 0.05). In postmenopausal women, serum PFOS was negatively associated with TFBMD and FNBMD, and PFNA was negatively associated with TFBMD, FNBMD, and LSBMD (all p < 0.05). With one log unit increase in serum PFOA, PFHxS, and PFNA, osteoporosis prevalence in women increased as follows: [adjusted odds ratios (aORs)] 1.84 (95% CI: 1.17, 2.905), 1.64 (95% CI: 1.14, 2.38), and 1.45 (95% CI: 1.02, 2.05), respectively. In women, the prevalence of osteoporosis was significantly higher in the highest versus the lowest quartiles of PFOA, PFHxS, and PFNA, with aORs of 2.59 (95% CI: 1.01, 6.67), 13.20 (95% CI: 2.72, 64.15), and 3.23 (95% CI: 1.44, 7.21), respectively, based on 77 cases in the study sample. CONCLUSION: In a representative sample of the U.S. adult population, serum PFAS concentrations were associated with lower bone mineral density, which varied according to the specific PFAS and bone site assessed. Most associations were limited to women. Osteoporosis in women was also associated with PFAS exposure, based on a small number of cases. CITATION: Khalil N, Chen A, Lee M, Czerwinski SA, Ebert JR, DeWitt JC, Kannan K. 2016. Association of perfluoroalkyl substances, bone mineral density, and osteoporosis in the U.S. population in NHANES 2009-2010. Environ Health Perspect 124:81-87; http://dx.doi.org/10.1289/ehp.1307909.

Bisphenol A and cardiometabolic risk factors in obese children.

BACKGROUND AND OBJECTIVE: Bisphenol-A (BPA) is an endocrine disruptor (ED) that has been associated with obesity and metabolic changes in liver in humans. Non-alcoholic fatty liver disease (NAFLD) affects 40% of all obese children in the United States. Association of BPA with NAFLD in children is poorly understood. We investigated if BPA might play a role. METHODS: In a cross sectional study of 39 obese and overweight children aged 3-8 years enrolled from the Children Medical Center of Dayton, Ohio, anthropometric, clinical and biochemical assessment of serum samples were conducted. Urinary BPA was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and was adjusted for urinary creatinine BPA (creatinine) using linear regression and spline analyses. RESULTS: Higher urinary BPA (creatinine) concentration in overweight and obese children was associated with increasing free thyroxine. In male children BPA (creatinine) decreased with age, and was associated with elevated liver enzyme aspartate aminotransferase and diastolic blood pressure. The association of BPA (creatinine) persisted even after adjusting for age and ethnicity. Also in males, BPA concentration unadjusted for creatinine was significantly associated with serum fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR) showing non-monotonic exposure-response relationship. CONCLUSION: Urinary BPA in obese children, at least in males is associated with adverse liver and metabolic effects, and high diastolic blood pressure.

Gene-by-age effects on BMI from birth to adulthood: the Fels Longitudinal Study.

OBJECTIVES: Genome wide association studies have shown 32 loci to influence BMI in European-American adults but replication in other studies is inconsistent and may be attributed to gene-by-age effects. The aims of this study were to determine if the influence of the summed risk score of these 32 loci (GRS) on BMI differed across age from birth to 40 years, and to determine if additive genetic effects other than those in the GRS differed by age. METHODS: Serial measures of BMI were calculated at 0, 1, 3, 6, 9, 12, 18, and 28 months, and 4, 7, 11, 15, 19, 23, 30, and 40 years for 1,176 (605 females, 571 males) European-American participants in the Fels Longitudinal Study. SOLAR was used for genetic analyses. RESULTS: GRS was significant (P < 0.05) at ages: 6, 9 months, 4-15 years, and 23-40 years. Remaining additive genetic effects independently influenced BMI (P < 5.3 × 10(-5) , 0.40 < h(2) < 0.76). Some genetic correlations between ages were not significant. Differential GRS effects did not retain significance after multiple comparisons adjustments. CONCLUSIONS: While well-known BMI variants do not appear to have significant differential effects, other additive genes differ over the lifespan.

The positive association of obesity variants with adulthood adiposity strengthens over an 80-year period: a gene-by-birth year interaction.

OBJECTIVE: To test the hypothesis that the statistical effect of obesity-related genetic variants on adulthood adiposity traits depends on birth year. METHODS: The study sample included 907 related, non-Hispanic White participants in the Fels Longitudinal Study, born between 1901 and 1986, and aged 25-64.99 years (474 females; 433 males) at the time of measurement. All had both genotype data from which a genetic risk score (GRS) composed of 32 well-replicated obesity-related common single nucleotide polymorphisms was created, and phenotype data [including body mass index (BMI), waist circumference, and the sum of four subcutaneous skinfolds]. Maximum likelihood-based variance components analysis was used to estimate trait heritabilities, main effects of GRS and birth year, GRS-by-birth year interaction, sex, and age. RESULTS: Positive GRS-by-birth year interaction effects were found for BMI (p < 0.001), waist circumference (p = 0.007), and skinfold thickness (p < 0.007). For example, each one-allele increase in GRS was estimated to result in a 0.16 increase in BMI among males born in 1930 compared to a 0.47 increase among those born in 1970. CONCLUSIONS: These novel findings suggest the influence of common obesity susceptibility variants has increased during the obesity epidemic.

Systematic examination of infant size and growth metrics as risk factors for overweight in young adulthood.

OBJECTIVE: To systematically examine infant size and growth, according to the 2006 WHO infant growth standards, as risk factors for overweight status in young adulthood in a historical cohort. Specifically, to assess: Whether accounting for length (weight-for-length) provides a different picture of risk than weight-for-age, intervals of rapid growth in both weight-for-age and weight-for-length metrics, and what particular target ages for infant size and intervals of rapid growth associate most strongly with overweight as a young adult. PATIENTS/METHODS: Data analysis of 422 appropriate for gestational age white singleton infants enrolled in the Fels Longitudinal Study. Odds ratios (OR) for overweight and obesity in young adulthood (age 20-29) were calculated using logistic regression models for the metrics at each target age (0, 1, 3, 6, 9, 12, 18, 24 months) comparing ≥85(th) v. <85(th) percentile, as well as rapid growth (Δ≥0.67 Z-score) through target age intervals. Models accounted for both maternal and paternal BMI. RESULTS: Infants ≥85(th) percentile of weight-for-age at each target age (except 3 months) had a greater odds of being overweight as a young adult. After accounting for length (weight-for-length) this association was limited to 12, and 18 months. Rapid weight-for-age growth was infrequently associated with overweight as a young adult. Rapid weight-for-length growth from 0 to 24 months, 1 to 6, 9, 12, 18, and 24 months and from 3 to 9, 12, 18, and 24 months was strongly associated with overweight status as a young adult. CONCLUSIONS: The WHO weight-for-length metric associates differently with risk of being overweight as a young adult compared to weight-for-age. Intervals of rapid weight-for-length growth ranging from months (0-24), (1-12, 18, and 24) and (3-9, and 12) displayed the largest OR for being overweight as a young adult.

Wrist breadth and homeostasis model assessment of insulin resistance in youth: the Fels Longitudinal Study.

OBJECTIVES: There is biological crosstalk between insulin signaling and bone remodeling pathways, and wrist circumference and bone area were recently found to associate with insulin resistance independent of body mass index (BMI) in overweight/obese children. We aimed to expand on this work by using more specific measures of adiposity for adjustment and examining children with broader range of BMI. METHODS: We used serial data (1,051 total measures) on 313 non-Hispanic white youth (ages 8-18 y) from the Fels Longitudinal Study with homeostasis model assessment of insulin resistance (HOMA-IR) as the outcome. Internal standard deviation score (SDS) for wrist breadth was evaluated as a predictor of HOMA-IR (log-transformed) before and after adjusting for internal-sample SDSs for BMI, waist circumference (WC), and total body fat (TBF) from dual energy X-ray absorptiometry, in addition to age, sex, Tanner stage, and birth year, using generalized estimating equations. RESULTS: Before additional adiposity adjustment, we found a significant positive association between wrist breadth SDS and log-transformed HOMA-IR (ß = 0.13; 95%CI: 0.09-0.17), which remained significant after adjusting for TBF SDS (ß = 0.09; 95%CI: 0.05-0.13; P < 0.001), BMI SDS (ß = 0.06; 95%CI: 0.02-0.10; P = 0.007), and WC SDS (ß = 0.06; 95%CI: 0.02-0.09; P = 0.005). CONCLUSIONS: Further work is needed to determine whether simple frame size measures such as wrist breadth may be useful markers of metabolic risk.

Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course.

Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10⁻8) near FTO (P = 3.72 × 10⁻²³), TMEM18 (P = 3.24 × 10⁻¹7), MC4R (P = 4.41 × 10⁻¹7), TNNI3K (P = 4.32 × 10⁻¹¹), SEC16B (P = 6.24 × 10⁻9), GNPDA2 (P = 1.11 × 10⁻8) and POMC (P = 4.94 × 10⁻8) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10⁻5 after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages.