DNA methylation near MAD1L1, KDM2B, and SOCS3 mediates the effect of socioeconomic status on elevated body mass index in African American adults.

Obesity and poverty disproportionally affect African American persons. Epigenetic mechanisms could partially explain the association between socioeconomic disadvantage and body mass index (BMI). We examined the extent to which epigenetic mechanisms mediate the effect of socioeconomic status (SES) on BMI. Using data from African American adults from the Atherosclerosis Risk in Communities (ARIC) Study (n = 2664, mean age = 57 years), education, income, and occupation were used to create a composite SES score at visit 1 (1987-1989). We conducted two methylation-wide association analyses to identify associations between SES (visit 1), BMI and cytosine-phosphate-guanine (CpG) sites measured at a subsequent visit (1990-1995). We then utilized structural equation modeling (SEM) to test whether identified sites mediated the association between earlier SES and BMI in sex-stratified models adjusted for demographic and risk factor covariates. Independent replication and meta-analyses were conducted using the Jackson Heart Study (JHS, n = 874, mean age 51 years, 2000-2004). Three CpG sites near MAD1L1, KDM2B, and SOCS3 (cg05095590, cg1370865, and cg18181703) were suggestively associated (P-value < 1.3×10-5) in ARIC and at array-wide significance (P-value < 1.3×10-7) in a combined meta-analysis of ARIC with JHS. SEM of these three sites revealed significant indirect effects in females (P-value < 5.8×10-3), each mediating 7%-20% of the total effect of SES on BMI. Nominally significant indirect effects were observed for two sites near MAD1L1 and KDM2B in males (P-value < 3.4×10-2), mediating -17 and -22% of the SES-BMI effect. These results provide further evidence that epigenetic modifications may be a potential pathway through which SES may "get under the skin" and contribute to downstream health disparities.

Identification of type 2 diabetes loci in 433,540 East Asian individuals.

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

Disordered eating and cardiometabolic risk factors in Chinese women: evidence from the China Health and Nutrition Survey.

Disordered eating (DE) is associated with elevated cardiometabolic risk (CMR) factors, yet little is known about this association in non-Western countries. We examined the association between DE characteristics and CMR and tested the potential mediating role of BMI. This cross-sectional study included 2005 Chinese women (aged 18-50 years) from the 2015 China Health and Nutrition Survey. Loss of control, restraint, shape concern and weight concern were assessed using selected questions from the SCOFF questionnaire and the Eating Disorder Examination-Questionnaire. Eight CMR were measured by trained staff. Generalised linear models examined associations between DE characteristics with CMR accounting for dependencies between individuals in the same household. We tested whether BMI potentially mediated significant associations using structural equation modelling. Shape concern was associated with systolic blood pressure (ß (95 % CI) 0·06 (0·01, 0·10)), diastolic blood pressure (DBP) (0·07 (95 % CI 0·03, 0·11)) and high-density lipoprotein (HDL)-cholesterol (-0·08 (95 % CI -0·12, -0·04)). Weight concern was associated with DBP (0·06 (95 % CI 0·02, 0·10)), triglyceride (0·06 (95 % CI 0·02, 0·10)) and HDL-cholesterol (-0·10 (95 % CI -0·14, -0·07)). Higher scores on DE characteristics were associated with higher BMI, and higher BMI was further associated with lower HDL-cholesterol and higher other CMR. In summary, we observed significant associations between shape and weight concerns with some CMR in Chinese women, and these associations were potentially partially mediated by BMI. Our findings suggest that prevention and intervention strategies focusing on addressing DE could potentially help reduce the burden of CMR in China, possibly through controlling BMI.

Accelerometer-measured physical activity and postmenopausal breast cancer incidence in the Women's Health Accelerometry Collaboration.

BACKGROUND: Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC risk among women in the Women's Health Accelerometry Collaboration (WHAC). METHODS: The WHAC comprised 21,089 postmenopausal women (15,375 from the Women's Health Study [WHS]; 5714 from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study [OPACH]). Women wore an ActiGraph GT3X+ on the hip for ≥4 days and were followed for 7.4 average years to identify physician-adjudicated in situ (n = 94) or invasive (n = 546) BCs. Multivariable stratified Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles of physical activity measures in association with incident BC overall and by cohort. Effect measure modification was examined by age, race/ethnicity, and body mass index (BMI). RESULTS: In covariate-adjusted models, the highest (vs. lowest) tertiles of VM/15s, TPA, LPA, and MVPA were associated with BC HRs of 0.80 (95% CI, 0.64-0.99), 0.84 (95% CI, 0.69-1.02), 0.89 (95% CI, 0.73-1.08), and 0.81 (95% CI, 0.64-1.01), respectively. Further adjustment for BMI or physical function attenuated these associations. Associations were more pronounced among OPACH than WHS women for VM/15s, MVPA, and TPA; younger than older women for MVPA; and women with BMI ≥30 than <30 kg/m2 for LPA. CONCLUSION: Greater levels of accelerometer-assessed PA were associated with lower BC risk. Associations varied by age and obesity and were not independent of BMI or physical function.

Association Between Mid-arm Muscle Circumference and Cognitive Function: A Longitudinal Study of Chinese Adults.

BACKGROUND: Dementia affects 55 million people worldwide and low muscle mass may be associated with cognitive decline. Mid-arm muscle circumference (MAMC) correlates with dual-energy Xray absorptiometry and bioelectrical impedance analyses, yet are not routinely available. Therefore, we examined the association between MAMC and cognitive performance in older adults. METHODS: We included community-dwelling adults ≥55 years from the China Health and Nutrition Survey. Cognitive function was estimated based on a subset of the modified Telephone Interview for Cognitive Status (0-27, low-high) during years (1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, 2018). A multivariable linear mixed-effects model was used to test whether MAMC was associated with rate of cognitive decline across age groups and cognitive function overall. RESULTS: Of 3702 adults (53% female, 63.2 ± 7.3 years), mean MAMC was 21.4 cm ± 3.0 and baseline cognitive score was 13.6 points ±6.6. We found no evidence that the age-related rate of cognitive decline differed by MAMC (P = .77). Declines between 5-year age groups ranged from -.80 [SE (standard error) .18] to -1.09 [.22] for those at a mean MAMC, as compared to -.86 [.25] to -1.24 [.31] for those at a 1 MAMC 1 standard deviation above the mean. Higher MAMC was associated with better cognitive function with .13 [.06] higher scores for each corresponding 1 standard deviation increase in MAMC across all ages. CONCLUSION: Higher MAMC at any age was associated with better cognitive performance in older adults. Understanding the relationship between muscle mass and cognition may identify at-risk subgroups needing targeted interventions to preserve cognition.

The Carolina hysterectomy cohort (CHC): a novel case series of reproductive-aged hysterectomy patients across 10 hospitals in the US south.

BACKGROUND: Hysterectomy is a common surgery among reproductive-aged U.S. patients, with rates highest among Black patients in the South. There is limited insight on causes of these racial differences. In the U.S., electronic medical records (EMR) data can offer richer detail on factors driving surgical decision-making among reproductive-aged populations than insurance claims-based data. Our objective in this cohort profile paper is to describe the Carolina Hysterectomy Cohort (CHC), a large EMR-based case-series of premenopausal hysterectomy patients in the U.S. South, supplemented with census and surgeon licensing data. To demonstrate one strength of the data, we evaluate whether patient and surgeon characteristics differ by insurance payor type. METHODS: We used structured and abstracted EMR data to identify and characterize patients aged 18-44 years who received hysterectomies for non-cancerous conditions between 10/02/2014-12/31/2017 in a large health care system comprised of 10 hospitals in North Carolina. We used Chi-squared and Kruskal Wallis tests to compare whether patients' socio-demographic and relevant clinical characteristics, and surgeon characteristics differed by patient insurance payor (public, private, uninsured). RESULTS: Of 1857 patients (including 55% non-Hispanic White, 30% non-Hispanic Black, 9% Hispanic), 75% were privately-insured, 17% were publicly-insured, and 7% were uninsured. Menorrhagia was more prevalent among the publicly-insured (74% vs 68% overall). Fibroids were more prevalent among the privately-insured (62%) and the uninsured (68%). Most privately insured patients were treated at non-academic hospitals (65%) whereas most publicly insured and uninsured patients were treated at academic centers (66 and 86%, respectively). Publicly insured and uninsured patients had higher median bleeding (public: 7.0, uninsured: 9.0, private: 5.0) and pain (public: 6.0, uninsured: 6.0, private: 3.0) symptom scores than the privately insured. There were no statistical differences in surgeon characteristics by payor groups. CONCLUSION: This novel study design, a large EMR-based case series of hysterectomies linked to physician licensing data and manually abstracted data from unstructured clinical notes, enabled identification and characterization of a diverse reproductive-aged patient population more comprehensively than claims data would allow. In subsequent phases of this research, the CHC will leverage these rich clinical data to investigate multilevel drivers of hysterectomy in an ethnoracially, economically, and clinically diverse series of hysterectomy patients.

Infant Growth Trajectories and Lipid Levels in Adolescence: Evidence From a Chilean Infancy Cohort.

Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European-ancestry cohorts with few repeated observations in early infancy. We investigated the association between infant growth before 6 months and lipid levels in adolescents in a Hispanic/Latino cohort. We characterized infant growth from birth to 5 months in male (n = 311) and female (n = 285) infants from the Santiago Longitudinal Study (1991-1996) using 3 metrics: weight (kg), length (cm), and weight-for-length (g/cm). Superimposition by translation and rotation (SITAR) and latent growth mixture models (LGMMs) were used to estimate the association between infant growth characteristics and lipid levels at age 17 years. We found a positive relationship between the SITAR length velocity parameter before 6 months of age and high-density lipoprotein cholesterol levels in adolescence (11.5, 95% confidence interval; 3.4, 19.5), indicating higher high-density lipoprotein cholesterol levels occurring with faster length growth. The strongest associations from the LGMMs were between higher low-density lipoprotein cholesterol and slower weight-for-length growth, following a pattern of associations between slower growth and adverse lipid profiles. Further research in this window of time can confirm the association between early infant growth as an exposure and adolescent cardiovascular disease risk factors.

Development of an algorithm to assess unmeasured symptom severity in gynecologic care.

BACKGROUND: Healthcare disparities research is often limited by incomplete accounting for differences in health status by populations. In the United States, hysterectomy shows marked variation by race and geography, but it is difficult to understand what factors cause these variations without accounting for differences in the severity of gynecologic symptoms that drive the decision-making for hysterectomy. OBJECTIVE: This study aimed to demonstrate a method for using electronic health record-derived data to create composite symptom severity indices to more fully capture relevant markers that influence the decision for hysterectomy. STUDY DESIGN: This was a retrospective cohort study of 1993 women who underwent hysterectomy between April 4, 2014, and December 31, 2017, from 10 hospitals and >100 outpatient clinics in North Carolina. Electronic health record data, including billing, pharmacy, laboratory data, and free-text notes, were used to identify markers of 3 common indications for hysterectomy: bulk symptoms (pressure from uterine enlargement), vaginal bleeding, and pelvic pain. To develop weighted symptom indices, we finalized a scoring algorithm based on the relationship of each marker to an objective measure, in combination with clinical expertise, with the goal of composite symptom severity indices that had sufficient variation to be useful in comparing different patient groups and allow discrimination among severe symptoms of bulk, bleeding, or pain. RESULTS: The ranges of symptom severity scores varied across the 3 indices, including composite bulk score (0-14), vaginal bleeding score (0-44), and pain score (0-30). The mean values of each composite symptom severity index were greater for those who had diagnostic codes for vaginal bleeding, bulk symptoms, or pelvic pain, respectively. However, each index demonstrated a variation across the entire group of hysterectomy cases and identified symptoms that ranged in severity among those with and without the target diagnostic codes. CONCLUSION: Leveraging multisource data to create composite symptom severity indices provided greater discriminatory power to assess common gynecologic indications for hysterectomy. These methods can improve the understanding in healthcare use in the setting of long-standing inequities and be applied across populations to account for previously unexplained variations across race, geography, and other social indicators.

Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents.

BACKGROUND: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors. METHODS: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. RESULTS: We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. CONCLUSIONS: The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers. IMPACT: This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

Predictors and Effects of Participation in Peer Support: A Prospective Structural Equation Modeling Analysis.

BACKGROUND: Peer support provides varied health benefits, but how it achieves these benefits is not well understood. PURPOSE: Examine a) predictors of participation in peer support interventions for diabetes management, and b) relationship between participation and glycemic control. METHODS: Seven peer support interventions funded through Peers for Progress provided pre/post data on 1,746 participants' glycemic control (hemoglobin A1c), contacts with peer supporters as an indicator of participation, health literacy, availability/satisfaction with support for diabetes management from family and clinical team, quality of life (EQ-Index), diabetes distress, depression (PHQ-8), BMI, gender, age, education, and years with diabetes. RESULTS: Structural equation modeling indicated a) lower levels of available support for diabetes management, higher depression scores, and older age predicted more contacts with peer supporters, and b) more contacts predicted lower levels of final HbA1c as did lower baseline levels of BMI and diabetes distress and fewer years living with diabetes. Parallel effects of contacts on HbA1c, although not statistically significant, were observed among those with baseline HbA1c values > 7.5% or > 9%. Additionally, no, low, moderate, and high contacts showed a significant linear, dose-response relationship with final HbA1c. Baseline and covariate-adjusted, final HbA1c was 8.18% versus 7.86% for those with no versus high contacts. CONCLUSIONS: Peer support reached/benefitted those at greater disadvantage. Less social support for dealing with diabetes and higher PHQ-8 scores predicted greater participation in peer support. Participation in turn predicted lower HbA1c across levels of baseline HbA1c, and in a dose-response relationship across levels of participation.

Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: The Santiago Longitudinal Study.

BACKGROUND AND AIMS: Adipose tissue secretes adipokines such as adiponectin and leptin, playing important roles in energy metabolism. The longitudinal associations between such adipokines and body fat accumulation have not been established, especially during adolescence and young adulthood and in diverse populations. The study aims to assess the longitudinal association between body fat measured with dual X-ray absorptiometry and plasma adipokines from adolescence to young adulthood. METHODS AND RESULTS: Among Hispanic/Latino participants (N = 537) aged 16.8 (SD: 0.3) years of the Santiago Longitudinal Study, we implemented structural equation modeling to estimate the sex-specific associations between adiposity (body fat percent (BF%) and proportion of trunk fat (PTF)) and adipokines (adiponectin and leptin levels) during adolescence (16 y) and these values after 6 years of follow-up (22 y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16 y BF% and 22 y leptin levels (ß (SE): 0.58 (0.06) for females; 0.53 (0.05) for males), between 16 y PTF and 22 y adiponectin levels (ß (SE): -0.31 (0.06) for females; -0.18 (0.06) for males) and between 16 y adiponectin levels and 22 y BF% (ß (SE): 0.12 (0.04) for both females and males). CONCLUSION: We observed dynamic relationships between adiposity and adipokines levels from late adolescence to young adulthood in a Hispanic/Latino population further demonstrating the importance of this period of the life course in the development of obesity.

Characterizing the urban diet: development of an urbanized diet index.

BACKGROUND: In recent decades China has experienced rapid urbanization leading to a major nutrition transition, with increased refined carbohydrates, added sweeteners, edible oils, and animal-source foods, and reduced legumes, vegetables, and fruits. These changes have accompanied increased prevalence of cardiometabolic disease (CMD). There is no single dietary measure that summarizes the distinct food changes across regions and levels of urbanization. METHODS: Using a sample of adults (≥18 years) in the 2015 wave of the China Health and Nutrition Survey (CHNS; n = 14,024), we selected literature-based candidate dietary variables and tested their univariate associations with overall and within-region urbanization. Using iterative exclusion of select diet-related variables, we created six potential urbanized diet indices, which we examined relative to overall urbanization to select a final urbanized diet index based on a priori considerations, strength of association with urbanization, and minimal missingness. We tested stability of the final urbanized diet index across sociodemographic factors. To examine whether our new measure reflected health risk, we used mixed effects logistic regression models to examine associations between the final urbanized diet index and CMD risk factors - hypertension (HTN), overweight, and type 2 diabetes mellitus (T2DM), adjusting for sociodemographics, overall urbanization, physical activity, and including random intercepts to account for correlation at community and household level. RESULTS: We identified a final urbanized diet index that captured dietary information unique to consumption of an urbanized diet and performed well across regions. We found a positive association (R2 = 0.17, 0.01 SE) between the final urbanized diet index and overall urbanization in the fully adjusted model. The new measure was negatively associated with HTN [OR (95% CI) = 0.93 (0.88-0.99)] and positively associated with T2D [OR = 1.13; 1.05-1.21] in minimally adjusted models, but not in the fully adjusted models. CONCLUSION: We derived an urbanized diet index that captured dietary urbanization that was distinct from overall urbanization and performed well across all regions of China. This urbanized diet index provides an alternative to measures of traditional versus urbanized diet that vary across regions due to different cultural dietary traditions. In addition, the new measure is best used in combination with diet quality measures, sociodemographic, and lifestyle measures to examine distinct pathways from urbanization to health in urbanizing countries.

Urbanization in China is associated with pronounced perturbation of plasma metabolites.

INTRODUCTION: Urbanization is associated with major changes in environmental and lifestyle exposures that may influence metabolic signatures. OBJECTIVES: We investigated cross-sectional urban and rural differences in plasma metabolome analyzed by liquid chromatography/mass spectrometry platform in 500 Chinese adults aged 25-68 years from two neighboring southern Chinese provinces. METHODS: We first examined the overall metabolome differences by urban and rural residential location, using Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) and random forest classification. We then tested the association between urbanization status and individual metabolites using a linear regression adjusting for age, sex, and province and conducted pathway analysis (Fisher's exact test) to identify metabolic pathways differed by urbanization status. RESULTS: We observed distinct overall metabolome by urbanization status in OPLS-DA and random forest classification. Using linear regression, out of a total of 1108 unique metabolite features identified in this sample, we found that 266 metabolites were differed by urbanization status (positive false discovery rate-adjusted p-value, q-value < 0.05). For example, the following metabolites were positively associated with urbanization status: caffeine metabolites from xanthine metabolism, hazardous pollutants like 4-hydroxychlorothalonil and perfluorooctanesulfonate, and metabolites implicated in cardiometabolic diseases, such as branched-chain amino acids. In pathway analysis, we found that xanthine metabolism pathways differed by urbanization status (q-value = 1.64E-04). CONCLUSION: We detected profound differences in host metabolites by urbanization status. Urban residents were characterized by metabolites signaling caffeine metabolism and toxic pollutants and metabolites on known pathways to cardiometabolic disease risks, compared to their rural counterparts. Our findings highlight the importance of considering urbanization in metabolomics analysis.

GIS-Based Home Neighborhood Food Outlet Counts, Street Connectivity, and Frequency of Use of Neighborhood Restaurants and Food Stores.

Researchers have linked neighborhood food availability to the overall frequency of using food outlets without noting if those outlets were within or outside of participants' neighborhoods. We aimed to examine the association of neighborhood restaurant and food store availability with frequency of use of neighborhood food outlets, and whether such an association was modified by neighborhood street connectivity using a large and diverse population-based cohort of middle-aged U.S. adults. We used self-reported frequency of use of fast food restaurants, sit-down restaurants, and grocery stores in respondents' home neighborhoods using data from the Coronary Artery Risk Development in Young Adults study Year 20 exam in 2005-2006 (n = 2860; Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA) and geographically matched GIS-measured neighborhood-level food resource, street, and U.S. Census data. We used mixed-effects logistic regression to examine the associations of the GIS-measured count of neighborhood fast food restaurants, sit-down restaurants, and grocery stores with self-reported frequency of using neighborhood restaurants and food stores and whether such associations differed by GIS-measured neighborhood street connectivity among those who perceived at least one such food outlet. In multivariate analyses, we observed a positive association between the GIS-measured count of neighborhood sit-down restaurants (OR = 1.02, 95% CI 1.00-1.04) and the self-reported frequency of using neighborhood sit-down restaurants. We observed no statistically significant association between GIS-measured count of neighborhood fast food restaurants and self-reported frequency of using neighborhood fast food restaurants, nor did we observe a statistically significant association between GIS-measured count of neighborhood grocery stores and self-reported frequency of using neighborhood grocery stores. We observed inverse associations between GIS-measured neighborhood street connectivity and the self-reported frequencies of using neighborhood fast food restaurants (OR = 0.42, 95% CI 0.26-0.68) and grocery stores (OR = - 2.26, 95% CI - 4.52 to - 0.01). Neighborhood street connectivity did not modify the association between GIS-measured neighborhood restaurant and food store count and the self-reported frequency of using neighborhood restaurants and food stores. Our findings suggest that, for those who perceived at least one sit-down restaurant in their neighborhood, individuals who have more GIS-measured sit-down restaurants in their neighborhoods reported more frequent use of sit-down restaurants than those whose neighborhoods contain fewer such restaurants. Our results also suggest that, for those who perceived at least one fast food restaurant in their neighborhood, individuals who live in neighborhoods with greater GIS-measured street connectivity reported less use of neighborhood fast food restaurants than those who live in neighborhoods with less street connectivity. The count of neighborhood sit-down restaurants and the connectivity of neighborhood street networks appear important in understanding the use of neighborhood food resources.

Effect of pregnancy on disease flares in patients with systemic lupus erythematosus.

OBJECTIVE: Prior studies found conflicting results about whether lupus is likely to flare during or after pregnancy. Using a large cohort of pregnant and non-pregnant women with lupus, we estimated the effect of pregnancy on disease flares in systemic lupus erythematosus. METHODS: Data were collected in the Hopkins Lupus Cohort 1987-2015. Women aged 14-45 years with >1 measurement of disease activity were included. The time-varying exposures were classified as pregnancy, postpartum or non-pregnant/non-postpartum periods. Flares were defined as: (1) change in Physician Global Assessment (PGA)≥1 from previous visit and (2) change in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)≥4 from previous visit. A stratified Cox model estimated HRs with bootstrap 95% CIs. RESULTS: There were 1349 patients, including 398 pregnancies in 304 patients. There was an increased rate of flare defined by PGA during pregnancy (HR: 1.59; 95% CI 1.27 to 1.96); however, this effect was modified by hydroxychloroquine (HCQ) use, with the HR of flares in pregnancy compared with non-pregnant/non-postpartum periods estimated to be 1.83 (95% CI 1.34 to 2.45) for patients with no HCQ use and 1.26 (95% CI 0.88 to 1.69) for patients with HCQ use. The risk of flare was similarly elevated among non-HCQ users in the 3 months postpartum, but not for women taking HCQ after delivery. CONCLUSIONS: Our study supports and extends previous findings that the incidence of flare is increased during pregnancy and within the 3 months postpartum. Continuing HCQ, however, appeared to mitigate the risk of flare during and after pregnancy.

Characterization of the contribution of shared environmental and genetic factors to metabolic syndrome methylation heritability and familial correlations.

BACKGROUND: Transgenerational epigenetic inheritance has been posited as a possible contributor to the observed heritability of metabolic syndrome (MetS). Yet the extent to which estimates of epigenetic inheritance for DNA methylation sites are inflated by environmental and genetic covariance within families is still unclear. We applied current methods to quantify the environmental and genetic contributors to the observed heritability and familial correlations of four previously associated MetS methylation sites at three genes (CPT1A, SOCS3 and ABCG1) using real data made available through the GAW20. RESULTS: Our findings support the role of both shared environment and genetic variation in explaining the heritability of MetS and the four MetS cytosine-phosphate-guanine (CpG) sites, although the resulting heritability estimates were indistinguishable from one another. Familial correlations by type of relative pair generally followed our expectation based on relatedness, but in the case of sister and parent pairs we observed nonsignificant trends toward greater correlation than expected, as would be consistent with the role of shared environmental factors in the inflation of our estimated correlations. CONCLUSIONS: Our work provides an interesting and flexible statistical framework for testing models of epigenetic inheritance in the context of human family studies. Future work should endeavor to replicate our findings and advance these methods to more robustly describe epigenetic inheritance patterns in human populations.

Trends in domain-specific physical activity and sedentary behaviors among Chinese school children, 2004-2011.

BACKGROUND: Dramatic increases in child overweight have occurred in China. A comprehensive look at trends in physical activity and sedentary behaviors among Chinese youth is needed. The study aimed to examine trends in domain-specific physical activity and sedentary behaviors, explore mean and distributional changes in predicted behaviors over time, and investigate how behaviors vary by residence. METHODS: Using 2004-2011 China Health and Nutrition Survey data, adjusted means for MET-hours/week from physical activity and hours/week from sedentary behaviors were determined for school children (6-18 years), stratifying by gender, age group, and residence. Physical activity domains included in-school physical activity, active leisure (out-of-school physical activity), active travel (walking or biking), and domestic activity (cooking, cleaning, and child care). For each physical activity domain, the MET-hours/week measure was determined from the total weekly time spent (hours) in domain-specific activities and corresponding MET-values using the Compendium of Energy Expenditures for Youth. Sedentary behaviors included television, computer use, homework, and other behaviors (board games, toys, extracurricular reading and writing). For each sedentary behavior, the hours/week measure was determined from total weekly time spent in specific sedentary behaviors. Residence groups included megacities (population ≥ 20million), cities/towns (300,000 ≤ population < 20million), and rural/suburban areas (population < 300,000). Repeated measure linear mixed and quantile regression models were used to predict adjusted means. RESULTS: Little change in physical activity behaviors occurred over time, with the exception of statistically significant trends toward increased domestic activity among male children (p < .05). Across all gender and age groups, statistically significant trends over time toward an average increase in computer use were seen (p < .01); these increases were largely driven by those ≥50th percentile on the distribution. Children living in megacities (versus rural areas) reported higher levels of physical activity, homework, and computer use. CONCLUSIONS: Intensified, systematic intervention and policy efforts promoting physical activity and reducing sedentary behaviors among children are needed.

Where Are Adults Active? An Examination of Physical Activity Locations Using GPS in Five US Cities.

Increasing physical activity (PA) at the population level requires appropriately targeting intervention development. Identifying the locations in which participants with various sociodemographic, body weight, and geographic characteristics tend to engage in varying intensities of PA as well as locations these populations underutilize for PA may facilitate this process. A visual location-coding protocol was developed and implemented in Google Fusion Tables and Maps using data from participants (N = 223, age 18-85) in five states. Participants concurrently wore ActiGraph GT1M accelerometers and Qstarz BT-Q1000X GPS units for 3 weeks to identify locations of moderate-to-vigorous (MVPA) or vigorous (VPA) bouts. Cochran-Mantel-Haenzel general association tests examined usage differences by participant characteristics (sex, age, race/ethnicity, education, body mass index (BMI), and recruitment city). Homes and roads encompassed >40% of bout-based PA minutes regardless of PA intensity. Fitness facilities and schools were important for VPA (19 and 12% of bout minutes). Parks were used for 13% of MVPA bout minutes but only 4% of VPA bout minutes. Hispanics, those without a college degree, and overweight/obese participants frequently completed MVPA bouts at home. Older adults often used roads for MVPA bouts. Hispanics, those with ≤high school education, and healthy/overweight participants frequently had MVPA bouts in parks. Applying a new location-coding protocol in a diverse population showed that adult PA locations varied by PA intensity, sociodemographic characteristics, BMI, and geographic location. Although homes, roads, and parks remain important locations for demographically targeted PA interventions, observed usage patterns by participant characteristics may facilitate development of more appropriately targeted interventions.

The association between urbanization and reduced renal function: findings from the China Health and Nutrition Survey.

BACKGROUND: While chronic kidney disease (CKD) is a growing public health concern in low- and middle-income countries, such as China, few studies have investigated the association between urbanization and the occurrence of CKD in those countries. METHODS: We investigated the association between urbanization and estimated glomerular filtration rate (eGFR), an important CKD risk marker. Data came from the China Health and Nutrition Survey wave 2009, in which we collected fasting serum, individual and household data along with community level urbanization data, which was used to derive a study-specific urbanization measure, in 218 communities across nine provinces. A total of 3644 men and 4154 women participants aged 18 years or older were included in the analysis. Reduced renal function was defined as eGFR of less than 60 mL/min/1.73 m2 measured using serum creatinine concentration (mg/dL). RESULTS: After adjusting for socio-demographic (e.g., age, education and household income), a sex-stratified multilevel logistic model revealed that living in a more urbanized community was associated with higher odds of reduced eGFR (odds ratio [OR] = 1.38 per one-standard deviation [SD] increase in the CHNS specific urbanization index, 95% confidence interval [CI] = 1.11-1.73 for men; OR = 1.35, 95% CI = 1.11-1.62 for women). After adjusting for behavioral variables (i.e., alcohol consumption, smoking, physical activity and diet), as well as obesity and cardiometabolic risk factors, the association was attenuated in men (OR = 1.25, 95% CI = 0.98-1.59), but remained statistically significant in women (OR = 1.24, 95% CI = 1.01-1.52). CONCLUSION: Our findings suggest that living in an urban environment is linked with higher odds of reduced renal function independently of behavioral and cardiometabolic risk factors, which have been shown to increase along with urbanization.