Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.

This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p < 1E-7) and 1,238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European and African descent, as defined by self-reported race/ethnicity. We found that five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log-normalized BMI in the WHI (80% training/20% testing). This model found that 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides and lower HDL cholesterol and LDL cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL cholesterol and lower glucose and triglycerides. This study confirmed 553 and identified 685 CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health, suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.

Characterisation and validation of lactation information from structured electronic health records for use in pharmacoepidemiological studies.

BACKGROUND: Breastfeeding information stored within electronic health records (EHR) has recently been used for pharmacoepidemiological research, however the data are primarily collected for clinical care. OBJECTIVES: To characterise breastfeeding information recorded in structured fields in EHR during infant and postpartum health care visits, and to assess the validity of lactation status based on EHR data versus maternal report at research study visits. METHODS: We assessed breastfeeding information recorded in structured fields in EHR from one health system for a subset of 211 patients who were also enrolled in a study on breast milk composition between 2014 and 2017 that required participants to exclusively breastfeed their infants until at least 1 month of age. We assessed the frequency of breastfeeding information in EHR during the first 12 months of age and compared lactation status based on EHR with maternal report at 1 and 6-month study visits (reference standard). RESULTS: The median number of breastfeeding records in the EHR per infant was six (interquartile range 3) with most observations clustering in the first few weeks of life and around well-infant visits. At the 6-month study visit, 93.8% of participants were breastfeeding and 80.1% were exclusively breastfeeding according to maternal report. Sensitivity of EHR data for identifying ever breastfeeding was at or near 100%, and sensitivity for identifying ever exclusive breastfeeding was 98.0% (95% CI: 95.0%, 99.2%). Sensitivities were 97.3% (95% CI: 93.9%, 98.9%) for identifying any breastfeeding and 94.4% (95% CI: 89.7%, 97.0%) for exclusive breastfeeding, and positive predictive values were 99.5% (95% CI: 97.0%, 99.9%) for any breastfeeding and 95.0% (95% CI: 90.4%, 97.4%) for exclusive breastfeeding. CONCLUSIONS: Breastfeeding information in structured EHR fields have the potential to accurately classify lactation status. The validity of these data should be assessed in populations with a lower breastfeeding prevalence.

Race, Ethnicity, and Cultural Identity Modify Postpartum Participation in the Minnesota WIC Program.

OBJECTIVE: To examine the racial, ethnic and cultural differences in postpartum participation of women who participated in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) during pregnancy by completing a retrospective analysis of observational data on 35,903 women who enrolled in Minnesota WIC during pregnancy, from April 2018 to March 2020. METHODS: Descriptive analyses were completed using chi-square tests of association to show differences in postpartum WIC participation by maternal demographics and health risk codes of the WIC participants. Binary logistic regression and multivariate logistic regression were used to obtain odds ratios to compare the likelihood of postpartum WIC participation across different races, ethnicities and cultural groups. RESULTS: Asian/Pacific Islander, East African, Hispanic, Hmong, Multigenerational Black, and Other Black pregnant participants were more likely than White participants to return to WIC postpartum (adjusted odds ratio (AOR) 2.54, 95% confidence interval (CI) 1.87-3.46; AOR 3.35, 95% CI 2.40-4.66; 1.30, 95% CI 1.10-1.54; AOR 6.76, 95% CI 4.39-10.42; AOR 1.40, 95% CI 1.11-1.77, AOR 1.52, 95% CI 1.26-1.83, respectively). American Indian pregnant participants were less likely than White participants to return to WIC postpartum (AOR 0.70, 95% CI 0.54-0.92). CONCLUSIONS FOR PRACTICE: These findings can help the Minnesota WIC program, as well as other WIC programs, better understand which cultural groups may need more specific outreach strategies to keep women participating in the program after giving birth. Further research is needed to understand why postpartum women choose to participate, or choose not to participate, in WIC.

Body composition after implementation of an enhanced parenteral nutrition protocol in the neonatal intensive care unit: a randomised pilot trial.

BACKGROUND: Very low birthweight (VLBW) infants are at risk for growth failure and poor neurodevelopment. Optimised parenteral nutrition may help promote optimal growth and development, but concerns that provision of enhanced nutrition may contribute to increased early adiposity and later metabolic disease remain. AIM: To determine associations between provision of an early enhanced parenteral nutrition protocol or standard parenteral nutrition protocol and growth and body composition for VLBW preterm infants in the neonatal intensive care unit. SUBJECTS: This is a secondary analysis of data from a clinical trial aimed at assessing the feasibility and safety of randomising VLBW preterm infants to Standard (n = 45) or Intervention (n = 42) parenteral nutrition groups between August 2017 and June 2019. METHODS: We evaluated associations between weekly infant growth and body composition measurements from n = 55 infants (Standard = 29, Intervention = 26) that were clinically stable enough to have body composition measurements taken before discharge using mixed effects linear regression models. RESULT: No statistically significant associations between nutrition group and infant growth or body composition measures were observed (p >.05). CONCLUSION: In this pilot trial, enhanced parenteral nutrition in the first week of life was not associated with significant differences in infant growth or body composition during hospitalisation.

Stability of Human-Milk Oligosaccharide Concentrations Over 1 Week of Lactation and Over 6 Hours Following a Standard Meal.

BACKGROUND: Our previous studies revealed that human-milk oligosaccharides (HMOs) have health benefits for nursing infants and their concentrations change dynamically over 24 mo of lactation. Yet, the extent to which HMOs vary over the short term (days) and in response to acute factors such as maternal diet is unclear. OBJECTIVE: The purpose of this study was to determine the stability of HMO concentrations over 7 d and in response to a standard meal and sugar-sweetened beverage (SSB) over 6 h. METHODS: In this ancillary study, lactating mothers were enrolled at 6 wk postpartum. Participants received in-person instructions and materials to complete procedures at home. In the 1-wk experiment (n = 11), mothers pumped a milk sample at 07:00 h for 7 consecutive days. In the 6-h experiment (n = 35), mothers pumped a milk sample after an overnight fast at 06:00 h and then consumed a standard meal plus SSB provided by the study team. Mothers pumped a milk sample every hour for 6 consecutive hours. Samples were analyzed for the 19 most abundant HMOs. Repeated-measures ANOVA was used to test changes in HMO concentrations over time, reported as F(dftime, dferror) = F value, P value. RESULTS: Concentrations of all assayed HMOs were stable over 7 consecutive days, including, for example, the most widely studied HMOs in relation to infant health: 2'-fucosyllactose (2'FL) [F(2,17) = 0.39, P = 0.65], disialyl-lacto-N-tetraose (DSLNT) [F(4, 37) = 0.60, P = 0.66], and lacto-N-neotetraose (LNnT) [F(3, 32) = 1.5, P = 0.23]. Concentrations of all assayed HMOs were stable in response to a standard meal plus SSB. For example, fasted baseline concentrations of 2'FL, DSLNT, and LNnT were 2310 ± 1620 µg/mL, 560 ± 290 µg/mL, and 630 ± 290 µg/mL, respectively, and there were no changes in 2'FL [F(4, 119) = 1.9, P = 0.13], DSLNT [F(4, 136) = 0.39, P = 0.83], and LNnT [F(4, 120) = 0.64, P = 0.63] over 6 consecutive hours. CONCLUSIONS: HMO concentrations are stable over 1 wk of lactation and are not acutely affected by a standard meal plus SSB in mothers.

Training the MCH workforce: the Time for Change is now.

INTRODUCTION: Maternal and child health (MCH) services are critical for vulnerable populations. Workforce shortages, poor retention, and gaps in necessary trainings impede the capacity of public health systems to address needs. This manuscript characterizes the current MCH workforce, MCH program applicants and graduates, and describe findings within a national context to devise elements of a recruitment and retention strategy. METHODS: Data were obtained for public health program applicants, first-destination employment outcomes, and worker perceptions and demographics. Data were stratified according to the MCH and total public health workforce and by local, state, and national totals. Data were characterized by degree type, discipline, demographics, and employment outcomes. RESULTS: MCH staff constitute 11% of the state and local governmental public health workforce. MCH staff are approximately as diverse, have higher educational attainment, and are more likely to hold nursing degrees than the rest of the public health workforce. Yet, just 14% of MCH staff hold any type of public health degree. The MCH pipeline from academia appears modestly sized, with approximately 5% of applicants between 2017 and 2021 applying to a MCH master's degree. DISCUSSION: The MCH workforce has a lower proportion of formal training or degrees in public health, though trends seem to indicate improvements. However, it is critical that a multi-faceted recruitment and retention strategy be coordinated by a broad range of stakeholders. These efforts will serve to improve the capability and capacity of the public health system to address critical needs of increasingly diverse MCH populations. SIGNIFICANCE: In order to modernize and reimagine the academic-public health pipeline, it is critical to better understand how many applicants and graduates exist within Maternal and Child Health programs across the US, and their characteristics. This manuscript connects that information with the most recently available public health workforce information on demographics, workplace perceptions, and intent to leave among staff at state and local health departments. Data presented in this paper allow the most comprehensive characterization of the MCH academia->practice pipeline to-date, identifies a fundamental disconnect in those career pathways, and offers options to repair that break.

Testing the Institute of Medicine (IOM) recommendations on maternal reproductive health and associated neonatal characteristics in a transitional, Mediterranean population.

BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are significant risk factors for maternal and neonatal health. AIM: To assess pre-pregnancy BMI and GWG during pregnancy and their association with different maternal and neonatal characteristics in the transitional Mediterranean population from the Eastern Adriatic islands. SUBJECTS AND METHODS: Two hundred and sixty-two mother-child dyads from the CRoatian Islands' Birth Cohort Study (CRIBS) were included in the study. Chi-square test, ANOVA, and regression analysis were used to test the association between selected characteristics. RESULTS: In total, 22% of women entered pregnancy as overweight/obese and 46.6% had excessive GWG. Pre-pregnancy overweight and obesity were significantly associated with elevated triglycerides uric acid levels, and decreased HDL cholesterol in pregnancy. Excessive GWG was associated with elevated fibrinogen and lipoprotein A levels. Women with high pre-pregnancy BMI and GWG values were more likely to give birth to babies that were large for gestational age (LGA), additionally confirmed in the multiple logistic regression model. CONCLUSION: High maternal pre-pregnancy BMI and excessive GWG were both significantly associated with deviated biochemical parameters and neonatal size. More careful monitoring of maternal nutritional status can lead to better pre- and perinatal maternal healthcare.

Maternal Dietary Intake of Total Fat, Saturated Fat, and Added Sugar Is Associated with Infant Adiposity and Weight Status at 6 mo of Age.

BACKGROUND: Whether current dietary guidelines are appropriate for pregnancy and lactation has not been well studied. Many women of reproductive age are not meeting recommendations for dietary components such as fat, added sugar, and fiber. OBJECTIVES: To assess associations between maternal dietary components during pregnancy and lactation and infant growth and adiposity at 6 mo of age. METHODS: Mother-infant dyads (n = 349) from the prospective, observational Mothers and Infants Linked for Healthy Growth study were included (100% fully breastfed for 1 mo; 75% to 6 mo). Daily intake of fat, fiber, and added sugar was obtained using the National Cancer Institute Diet History Questionnaire II during the third trimester of pregnancy and at 1 and 3 mo postpartum. Furthermore, intakes were categorized as meeting/exceeding 2015-2020 Dietary Guidelines for Americans. Multiple linear regression models adjusted for numerous potential confounders tested relations between dietary components and infant adiposity (via DXA) and growth parameters. Regression coefficients (ß) for continuous variables were expressed per SD to allow for comparison of effect sizes. RESULTS: Maternal intake of total fat and saturated fat was positively associated with infant percent body fat (%BF) (ß: 0.84 per SD, P = 0.04; ß: 0.96 per SD, P = 0.01, respectively). Added sugar intake was positively associated with infant weight-for-length z score (ß: 0.16 per SD, P = 0.02), and excessive added sugar intake was positively associated with %BF at 6 mo (ß: 0.75 per SD, P = 0.05). CONCLUSIONS: In a predominantly fully breastfeeding cohort of women, maternal intake of fat and added sugar during pregnancy and lactation were associated with small increases in infant adiposity and relative weight at 6 mo. Additional research is needed to determine if these relations persist later in infancy and if such elevations in adiposity are important for long-term obesity risk.

Infants exposed to antibiotics after birth have altered recognition memory responses at one month of age.

BACKGROUND: Neonatal exposure to antibiotics, in the absence of infection, results in abnormal learning and memory in animals and is linked to changes in gut microbes. The relevance of early-life antibiotic exposure to brain function in humans is not known. METHODS: Recognition memory was assessed at 1 month of age in 15 term-born infants exposed to antibiotics (with negative cultures) and 57 unexposed infants using event-related potentials (ERPs). Linear regression analysis, adjusting for covariates, was employed to compare groups with respect to ERP features representing early stimulus processing (P2 amplitude) and discrimination between mother and stranger voices. RESULTS: Infants exposed to antibiotics exhibited smaller P2 amplitudes for both voice conditions (p = 0.001), with greatest reductions observed for mother's voice in frontal and central scalp regions (p < 0.04). Infants exposed to antibiotics showed larger P2 amplitudes to stranger's as compared to mother's voice, a reversal of the typical response exhibited by unexposed infants. Abnormal ERP responses did not consistently correlate with increased inflammatory cytokines within the antibiotic-exposed group. CONCLUSIONS: Otherwise healthy infants exposed to antibiotics soon after birth demonstrated altered auditory processing and recognition memory responses, supporting the possibility of a microbiota-gut-brain axis in humans during early life. IMPACT: Infants exposed to antibiotics after birth demonstrate altered auditory processing and recognition memory responses at 1 month of age. Preclinical models support a role for gut microbiomes in modulating brain function and behavior, particularly in developing brains. This study is one of the first to explore the relevance of these findings for human infants. The findings of this study have implications for the management and follow-up of at-risk infants with exposure to gut-microbiome disrupting factors and lay foundation for future studies to further characterize the short- and long-term effects of gut microbiome perturbation on brain development.

Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study.

BACKGROUND: Short-duration exposure to ambient particulate matter (PM) air pollution is associated with cardiac autonomic dysfunction and prolonged ventricular repolarization. However, associations with sub-chronic exposures to coarser particulates are relatively poorly characterized as are molecular mechanisms underlying their potential relationships with cardiovascular disease. MATERIALS AND METHODS: We estimated associations between monthly mean concentrations of PM < 10 µm and 2.5-10 µm in diameter (PM10; PM2.5-10) with time-domain measures of heart rate variability (HRV) and QT interval duration (QT) among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities Study (nHRV = 82,107; nQT = 76,711). Then we examined mediation of the PM-HRV and PM-QT associations by DNA methylation (DNAm) at three Cytosine-phosphate-Guanine (CpG) sites (cg19004594, cg24102420, cg12124767) with known sensitivity to monthly mean PM concentrations in a subset of the participants (nHRV = 7,169; nQT = 6,895). After multiply imputing missing PM, electrocardiographic and covariable data, we estimated associations using attrition-weighted, linear, mixed, longitudinal models adjusting for sociodemographic, behavioral, meteorological, and clinical characteristics. We assessed mediation by estimating the proportions of PM-HRV and PM-QT associations mediated by DNAm. RESULTS: We found little evidence of PM-HRV association, PM-QT association, or mediation by DNAm. CONCLUSIONS: The findings suggest that among racially/ethnically and environmentally diverse U.S. populations, sub-chronic exposures to coarser particulates may not exert appreciable, epigenetically mediated effects on cardiac autonomic function or ventricular repolarization. Further investigation in better-powered studies is warranted, with additional focus on shorter duration exposures to finer particulates and non-electrocardiographic outcomes among relatively susceptible populations.

Integrating anthropometric and cardiometabolic health methods in stress, early experiences, and development (SEED) science.

Within Stress, Early Experiences, and Development (SEED) science, there is a growing body of research demonstrating complex associations not only between stress, development, and psychopathology, but also with chronic disease risk factors. We argue that it is important for SEED researchers to consider including child anthropometric and physical health measures to more comprehensively capture processes of risk and resilience. Broader adoption of harmonized anthropometry and health measures in SEED research will facilitate collaborations, yielding larger datasets for research in high-risk populations, and greater opportunity to replicate existing findings. In this review, we identify optimal anthropometric and cardiometabolic health measurement methods used from infancy through adolescence, including those that are low-burden and inexpensive. Methods covered include: waist, hip, and head circumference, height, length, weight, pubertal development, body composition, blood pressure, arterial stiffness, carotid intima media thickness, and serum measures of cardiometabolic risk and inflammation. We provide resources for SEED researchers to integrate these methods into projects or to better understand these methods when reading the literature as well as where to find collaborators for more in-depth studies incorporating these measures. With broader integration of psychological and physical health measures in SEED research, we can better inform theory and interventions to promote health and resilience in individuals who have experienced early stress.

Infant sex differences in human milk intake and composition from 1- to 3-month post-delivery in a healthy United States cohort.

BACKGROUND: Macronutrient composition of human milk differs by infant sex, but few studies have examined sex differences in other milk components, or their potential modification by maternal body mass index (BMI). AIM: We compared milk intake and human milk hormone and cytokine concentrations at 1- and 3-month post-delivery and tested infant sex by maternal BMI (OW/OB vs. NW) interactions. SUBJECTS AND METHOD: Data were analysed for 346 mother-infant dyads in the Mothers and Infants Linked for Healthy Growth (MILk) Study at 1- and 3-month post-delivery. Infant milk intake was estimated by the change in infant weight after test feedings. Concentrations of glucose, insulin, leptin, adiponectin, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured using ELISA. Multivariable linear regression and linear mixed models were used to estimate sex main effects and their interaction with maternal BMI. RESULTS: Mean glucose concentration at 1 month was 2.62 mg/dl higher for male infants, but no difference at 3 months was observed. Milk intake and concentrations for the other milk components were similar for males and females at both time points. Associations with infant sex did not differ significantly by maternal BMI. CONCLUSIONS: Among healthy United States mother-infant dyads, appetite, and growth-regulating factors in human milk did not differ significantly by infant sex.

Associations of breastfeeding or formula feeding with infant anthropometry and body composition at 6 months.

The objective of this study was to investigate the associations of mode of feeding with infant anthropometric and body composition variables at 6 months of age. We studied 259 infants whose exclusive mode of feeding (breast or formula) to 1 month was confirmed. Standard anthropometric characteristics of the infants (weight, length and weight-for-length z scores) were obtained, and body composition (total fat mass, fat-free mass, trunk fat mass and body fat percent) was measured using dual-energy X-ray absorptiometry (DXA) at 6 months (±12 days). General linear models were used to test the associations of mode of feeding with infant anthropometric and body composition variables at 6 months after adjustment for maternal and infant covariates. In this cohort of predominantly breastfed, White infants of highly educated mothers, fat-free mass was lower (P = .002), and trunk fat mass (P = .032) and body fat percent (P < .001) were greater in breastfed infants than in formula-fed infants at 6 months of age. After adjustment for covariates, total fat-free mass was significantly lower (ß = -372 g, [SE = 125, P = .003]), and body fat percent was significantly greater (ß = 3.30, [SE = 0.91, P < .001]) in breastfed infants than in formula-fed infants. No other significant associations were observed. These findings support those of previous studies reporting greater fat-free mass in formula-fed infants during the first 6 months of life. Additional research is warranted to explore whether differences in infant body composition by mode of feeding persist throughout the life course and to assess causality.

Carbohydrate composition in breast milk and its effect on infant health.

PURPOSE OF REVIEW: This narrative review presents the current state of available evidence regarding the role of breast milk carbohydrates on infant outcomes, with a primary focus on growth and body composition. RECENT FINDINGS: To date, there is a paucity of available data that exists in this realm. The current literature focuses on the role of two carbohydrate fractions in breast milk, and their relationships with infant outcomes in the first six months of life: oligosaccharides and fructose. A small but growing body of research indicates robust associations of both oligosaccharides and fructose in breast milk with infant weight and length, as well as bone, fat, and lean mass. There is also emerging evidence to support the role of these same carbohydrate fractions in breast milk in infant cognitive development. SUMMARY: The present state of the science suggests that oligosaccharides and fructose in breast milk play a role in infant growth and body composition and introduces intriguing associations of these two carbohydrate fractions with infant cognitive development as well.

Association between greater leg length and increased incidence of colorectal cancer: the atherosclerosis risk in communities (ARIC) study.

PURPOSE: Previous studies have reported that taller people have an increased risk of colorectal cancer (CRC). We examined the association of two height components-leg length and sitting height-with CRC risk in 14,532 individuals aged 45-64 years in the Atherosclerosis Risk in Communities study. METHODS: Anthropometrics were measured at baseline (1987-1989). Incident CRC cases (n = 382) were ascertained from 1987 to 2012. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios for CRC and colon cancer across quintiles of sex-specific leg length and sitting height. RESULTS: The highest (versus the lowest) quintile of leg length was associated with a 36% greater CRC risk (p-trend = 0.04), and 51% greater colon cancer risk (p-trend = 0.01). For the top four quintiles combined, risk was increased by 34% for CRC and by 45% for colon cancer versus the lowest quintile. Total height and sitting height were not significantly associated with CRC or colon cancer risk. A small number of cases (n = 57) limited our ability to conduct subgroup analyses for rectal cancer. CONCLUSIONS: A positive association of leg length with CRC and colon cancer risk suggests that biological mechanisms leading to greater leg length during puberty may explain the association between taller height and CRC.

Placental colonization with periodontal pathogens: the potential missing link.

Observational studies demonstrate that women with severe periodontitis have a higher risk of adverse pregnancy outcomes like preterm birth and low birthweight. Standard treatment for periodontitis in the form of scaling and root planing during the second trimester failed to reduce the risk of preterm or low birthweight. It is premature to dismiss the association between periodontitis and adverse pregnancy outcomes because one explanation for the failure of scaling and root planing to reduce the risk of adverse pregnancy outcomes is that periodontal pathogens spread to the placental tissue prior to periodontal treatment. In the placenta, orally derived organisms could cause direct tissue damage or mediate a maternal immune response that impairs the growth of the developing fetus. Sequencing studies demonstrate the presence of organisms derived from the oral microbiome in the placenta, but DNA-based sequencing studies should not be the only technique to evaluate the placental microbiome because they may not detect important shifts in the metabolic capability of the microbiome. In humans, polymerase chain reaction and histology have detected periodontal pathogens in placental tissue in association with multiple adverse pregnancy outcomes. We conclude that both placental and oral microbiomes may play a role in periodontitis-associated adverse pregnancy outcomes. However, the measure to determine the association between periodontal pathogens in the placenta and adverse pregnancy outcomes should be the amount and prevalence, not the mere presence of such microorganisms. Placental colonization with periodontal pathogens thus potentially represents the missing link between periodontitis and adverse pregnancy outcomes.

An Epigenome-Wide Association Study of Obesity-Related Traits.

We conducted an epigenome-wide association study on obesity-related traits. We used data from 2 prospective, population-based cohort studies: the Rotterdam Study (RS) (2006-2013) and the Atherosclerosis Risk in Communities (ARIC) Study (1990-1992). We used the RS (n = 1,450) as the discovery panel and the ARIC Study (n = 2,097) as the replication panel. Linear mixed-effect models were used to assess the cross-sectional associations between genome-wide DNA methylation in leukocytes and body mass index (BMI) and waist circumference (WC), adjusting for sex, age, smoking, leukocyte proportions, array number, and position on array. The latter 2 variables were modeled as random effects. Fourteen 5'-C-phosphate-G-3' (CpG) sites were associated with BMI and 26 CpG sites with WC in the RS after Bonferroni correction (P < 1.07 × 10-7), of which 12 and 13 CpGs were replicated in the ARIC Study, respectively. The most significant novel CpGs were located on the Musashi RNA binding protein 2 gene (MSI2; cg21139312) and the leucyl-tRNA synthetase 2, mitochondrial gene (LARS2; cg18030453) and were associated with both BMI and WC. CpGs at BRDT, PSMD1, IFI44L, MAP1A, and MAP3K5 were associated with BMI. CpGs at LGALS3BP, MAP2K3, DHCR24, CPSF4L, and TMEM49 were associated with WC. We report novel associations between methylation at MSI2 and LARS2 and obesity-related traits. These results provide further insight into mechanisms underlying obesity-related traits, which can enable identification of new biomarkers in obesity-related chronic diseases.

Cancer patterns in Hmong in Minnesota, 2000 to 2012.

BACKGROUND: Minnesota has the second largest Hmong population in the United States. The objective of the current study was to estimate the cancer incidence among Hmong individuals in Minnesota between 2000 and 2012 to determine targets for screening and interventions. METHODS: Cancer cases in Minnesota between 2000 and 2012 were obtained from the Minnesota Cancer Surveillance System, and proportional incidence ratios (PIRs) were calculated. The 2000 and 2010 US Census reports were used to obtain total population estimates. Age-adjusted cancer incidence rates (AAR) and 95% confidence intervals (95% CIs) were calculated for Hmong individuals, Asian/Pacific Islander individuals, and all Minnesotans using direct method and Poisson regression. RESULTS: Compared with all Minnesotans, the Hmong had elevated PIRs and AARs for malignancies related to infections, including nasopharyngeal, stomach, liver, and cervical cancers. The AAR ratios in Hmong versus all Minnesotans were found to be significantly increased for nasopharyngeal (AAR, 15.90; 95% CI, 9.48-26.68), stomach (AAR, 2.99; 95% CI, 2.06-4.33), liver (AAR, 1.77; 95% CI, 1.04-3.02), and cervical (AAR, 3.88; 95% CI, 2.61-5.77) cancers. The AARs in Hmong versus all Minnesotans were significantly lower for all-cause cancer (AAR, 0.39; 95% CI, 0.35-0.44); cancers of the breast, lung, and colorectum; melanoma; and non-Hodgkin lymphoma. Compared with Asian/Pacific Islander individuals, the rates in Hmong were significantly higher for melanoma and cervical cancer, with AAR ratios of 2.23 (95% CI, 1.09-4.56) and 1.59 (95% CI, 1.01-2.49), respectively. CONCLUSIONS: Compared with all Minnesotans, the Hmong have an increased incidence of cancers related to infectious agents. These findings indicate a need for cancer prevention and screening programs in this population.

Early body composition changes are associated with neurodevelopmental and metabolic outcomes at 4 years of age in very preterm infants.

BACKGROUND: Very preterm (VPT) infants are at-risk for altered growth, slower speed of processing (SOP), and hypertension. This study assesses the relationship between postnatal body composition (BC), neurodevelopment (indexed by SOP), and blood pressure (BP) in VPT infants. METHODS: Thirty-four VPT infants underwent weekly measurements and BC testing until discharge and post-discharge at 4 mos CGA and 4 yrs. At post-discharge visits, SOP was assessed using visual evoked potentials and the NIH Toolbox; BP was also measured. RESULTS: In-hospital rate of weight, length and fat-free mass (FFM) gains were associated with faster SOP at 4 yrs. Higher rate of gains in weight and FFM from discharge to 4 mos CGA were associated with faster SOP at 4 mos CGA, while higher fat mass (FM) gains during the same time were positively associated with BP at 4 yrs. BC at 4 yrs nor gains beyond 4 mos CGA were associated with outcomes. CONCLUSIONS: In VPT infants, early FFM gains are associated with faster SOP, whereas post-discharge FM gains are associated with higher BPs at 4 yrs. This shows birth to 4 mos CGA is a sensitive period for growth and its relation to neurodevelopmental and metabolic outcomes. Close monitoring and early nutritional adjustments to optimize quality of gains may improve outcomes.

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach.

BACKGROUND: The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. METHODS AND FINDINGS: We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. CONCLUSIONS: We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.