Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes.

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D). METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at visit 2), serum metabolome measured by untargeted metabolomics (624 metabolites; n=6198 at baseline), and associations between fiber-related gut bacteria and metabolites (n=804 at visit 2). We examined prospective associations of serum microbial-associated metabolites (n=3579 at baseline) with incident T2D over 6 years. RESULTS: We identified multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, Butyrivibrio, Faecalibacterium) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. We identified 159 metabolites associated with fiber intake, 47 of which were associated with incident T2D. We identified 18 of these 47 metabolites associated with the identified fiber-related bacteria, including several microbial metabolites (eg, indolepropionate and 3-phenylpropionate) inversely associated with the risk of T2D. Both Butyrivibrio and Faecalibacterium were associated with these favorable metabolites. The associations of fiber-related bacteria, especially Faecalibacterium and Butyrivibrio, with T2D were attenuated after further adjustment for these microbial metabolites. CONCLUSIONS: Among United States Hispanics/Latinos, dietary fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for T2D. These findings advance our understanding of the role of gut microbiota and microbial metabolites in the relationship between diet and T2D.

Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, and Cardiovascular Disease Risk in US Hispanics and Latinos: Results From HCHS/SOL.

BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.

Social and scientific motivations to move beyond groups in allele frequencies: The TOPMed experience.

For the genomics community, allele frequencies within defined groups (or "strata") are useful across multiple research and clinical contexts. Benefits include allowing researchers to identify populations for replication or "look up" studies, enabling researchers to compare population-specific frequencies to validate findings, and facilitating assessment of variant pathogenicity in clinical contexts. However, there are potential concerns with stratified allele frequencies. These include potential re-identification (determining whether or not an individual participated in a given research study based on allele frequencies and individual-level genetic data), harm from associating stigmatizing variants with specific groups, potential reification of race as a biological rather than a socio-political category, and whether presenting stratified frequencies-and the downstream applications that this presentation enables-is consistent with participants' informed consents. The NHLBI Trans-Omics for Precision Medicine (TOPMed) program considered the scientific and social implications of different approaches for adding stratified frequencies to the TOPMed BRAVO (Browse All Variants Online) variant server. We recommend a novel approach of presenting ancestry-specific allele frequencies using a statistical method based upon local genetic ancestry inference. Notably, this approach does not require grouping individuals by either predominant global ancestry or race/ethnicity and, therefore, mitigates re-identification and other concerns as the mixture distribution of ancestral allele frequencies varies across the genome. Here we describe our considerations and approach, which can assist other genomics research programs facing similar issues of how to define and present stratified frequencies in publicly available variant databases.

Cumulative All-Cause Mortality in Diverse Hispanic/Latino Adults : A Prospective, Multicenter Cohort Study.

BACKGROUND: All-cause mortality among diverse Hispanic/Latino groups in the United States and factors underlying mortality differences have not been examined prospectively. OBJECTIVE: To describe cumulative all-cause mortality (and factors underlying differences) by Hispanic/Latino background, before and during the COVID-19 pandemic. DESIGN: Prospective, multicenter cohort study. SETTING: Hispanic Community Health Study/Study of Latinos. PARTICIPANTS: 15 568 adults aged 18 to 74 years at baseline (2008 to 2011) of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other backgrounds from the Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California. MEASUREMENTS: Sociodemographic, acculturation-related, lifestyle, and clinical factors were assessed at baseline, and vital status was ascertained through December 2021 (969 deaths; 173 444 person-years of follow-up). Marginally adjusted cumulative all-cause mortality risks (11-year before the pandemic and 2-year during the pandemic) were examined using progressively adjusted Cox regression. RESULTS: Before the pandemic, 11-year cumulative mortality risks adjusted for age and sex were higher in the Puerto Rican and Cuban groups (6.3% [95% CI, 5.2% to 7.6%] and 5.7% [CI, 5.0% to 6.6%], respectively) and lowest in the South American group (2.4% [CI, 1.7% to 3.5%]). Differences were attenuated with adjustment for lifestyle and clinical factors. During the pandemic, 2-year cumulative mortality risks adjusted for age and sex ranged from 1.1% (CI, 0.6% to 2.0%; South American) to 2.0% (CI, 1.4% to 3.0%; Central American); CIs overlapped across groups. With adjustment for lifestyle factors, 2-year cumulative mortality risks were highest in persons of Central American and Mexican backgrounds and lowest among those of Puerto Rican and Cuban backgrounds. LIMITATION: Lack of data on race and baseline citizenship status; correlation between Hispanic/Latino background and site. CONCLUSION: Differences in prepandemic mortality risks across Hispanic/Latino groups were explained by lifestyle and clinical factors. Mortality patterns changed during the pandemic, with higher risks in persons of Central American and Mexican backgrounds than in those of Puerto Rican and Cuban backgrounds. PRIMARY FUNDING SOURCE: National Institutes of Health.

Sleep duration and brain MRI measures: Results from the SOL-INCA MRI study.

INTRODUCTION: Sleep duration has been associated with dementia and stroke. Few studies have evaluated sleep pattern-related outcomes of brain disease in diverse Hispanics/Latinos. METHODS: The SOL-INCA (Study of Latinos-Investigation of Neurocognitive Aging) magnetic resonance imaging (MRI) study recruited diverse Hispanics/Latinos (35-85 years) who underwent neuroimaging. The main exposure was self-reported sleep duration. Our main outcomes were total and regional brain volumes. RESULTS: The final analytic sample included n = 2334 participants. Increased sleep was associated with smaller brain volume (ßtotal_brain  = -0.05, p < 0.01) and consistently so in the 50+ subpopulation even after adjusting for mild cognitive impairment status. Sleeping >9 hours was associated with smaller gray (ßcombined_gray  = -0.17, p < 0.05) and occipital matter volumes (ßoccipital_gray  = -0.18, p < 0.05). DISCUSSION: We found that longer sleep duration was associated with lower total brain and gray matter volume among diverse Hispanics/Latinos across sex and background. These results reinforce the importance of sleep on brain aging in this understudied population. HIGHLIGHTS: Longer sleep was linked to smaller total brain and gray matter volumes. Longer sleep duration was linked to larger white matter hyperintensities (WMHs) and smaller hippocampal volume in an obstructive sleep apnea (OSA) risk group. These associations were consistent across sex and Hispanic/Latino heritage groups.

Psychosocial factors associated with 7-year change in cognition among middle-aged and older Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) and Sociocultural ancillary studies.

INTRODUCTION: Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos. METHODS: Data from the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL INCA) and Sociocultural studies were used (n = 2,155; ages ≥45 years). Psychosocial exposures included intrapersonal (ethnic identity, optimism, purpose in life), interpersonal (family cohesion, familism, social networks, social support), and social factors (ethnic discrimination, loneliness, subjective social status). Survey-linear regression models examined associations between psychosocial exposures and 7-year cognitive change (global cognition [GC], verbal learning, memory, word fluency [WF], and digit symbol substitution [DSS]). RESULTS: Familism predicted decline in GC, verbal learning, and memory; family cohesion predicted DSS decline; and loneliness predicted memory decline. Ethnic identity was protective against decline in GC and memory, optimism and social support were protective against decline in memory, and purpose in life was protective against WF decline. DISCUSSION: Psychosocial factors are differentially related to cognitive changes. Culturally relevant factors should be explored in Hispanic/Latino cognitive aging research. HIGHLIGHTS: Psychosocial factors are differentially related to cognitive changes in Latinos. Role of culturally relevant factors on cognition should be further explored. Familism predicted decline in global cognition, verbal learning, and memory. Ethnic identity predicted increase in global cognition and memory.

Connections between reproductive health and cognitive aging among women enrolled in the HCHS/SOL and SOL-INCA.

INTRODUCTION: Reproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women. METHODS: Participants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence). RESULTS: Younger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence. DISCUSSION: Several aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

Childhood and Life-Course Socioeconomic Position and Cognitive Function in the Adult Population of the Hispanic Community Health Study/Study of Latinos.

The Hispanic/Latino population experiences socioeconomic adversities across the lifespan and is at greater risk of cognitive impairment, yet little is known about the role of life-course socioeconomic position (SEP) in cognitive function in this population. Using baseline data (2008-2011) from adults (aged 45-74 years) of the Hispanic Community Health Study/Study of Latinos, we assessed the association between childhood SEP and socioeconomic mobility with cognitive function, and whether this association was mediated by midlife SEP. Childhood SEP was assessed using parental education. An index combining participants' education and household income represented midlife SEP. Socioeconomic mobility was categorized as stable low, downward or upward mobility, and stable high-SEP. Cognitive function measures were modeled using survey linear regression with inverse-probability weighting, accounting for covariates. We used mediation analysis to estimate the indirect effect of childhood SEP on cognition through midlife SEP. High childhood SEP was associated with global cognition in adulthood (coefficient for parental education beyond high school vs. less than high school = 0.26, 95% confidence interval: 0.15, 0.37). This association was partially mediated through midlife SEP (indirect effect coefficient = 0.16, 95% confidence interval: 0.15, 0.18). Low SEP through the life course was associated with the lowest cognitive function. This study provides evidence that life-course SEP influences cognitive performance in adulthood.

Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL.

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P < 1 × 10-6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (P < 0.05 and consistent direction of effect, and P < 5 × 10-8 after meta-analysis), including two for WHRadjBMI (rs13301996, rs79478137); one for WCadjBMI (rs3168072) and one for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI, 10 for WCadjBMI and 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity susceptibility that may be ancestry-specific.

A Gene-Acculturation Study of Obesity Among US Hispanic/Latinos: The Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: In the United States, Hispanic/Latino adults face a high burden of obesity; yet, not all individuals are equally affected, partly due in part to this ethnic group's marked sociocultural diversity. We sought to analyze the modification of body mass index (BMI) genetic effects in Hispanic/Latino adults by their level of acculturation, a complex biosocial phenomenon that remains understudied. METHODS: Among 11,747 Hispanic/Latinos adults in the Hispanic Community Health Study/Study of Latinos aged 18 to 76 years from four urban communities (2008-2011), we a) tested our hypothesis that the effect of a genetic risk score (GRS) for increased BMI may be exacerbated by higher levels of acculturation and b) examined if GRS acculturation interactions varied by gender or Hispanic/Latino background group. All genetic modeling controlled for relatedness, age, gender, principal components of ancestry, center, and complex study design within a generalized estimated equation framework. RESULTS: We observed a GRS increase of 0.34 kg/m 2 per risk allele in weighted mean BMI. The estimated main effect of GRS on BMI varied both across acculturation level and across gender. The difference between high and low acculturation ranged from 0.03 to 0.23 kg/m 2 per risk allele, but varied across acculturation measure and gender. CONCLUSIONS: These results suggest the presence of effect modification by acculturation, with stronger effects on BMI among highly acculturated individuals and female immigrants. Future studies of obesity in the Hispanic/Latino community should account for sociocultural environments and consider their intersection with gender to better target obesity interventions.

Risk Factors for Cardiovascular Disease: Knowledge Gained from the Hispanic Community Health Study/Study of Latinos.

PURPOSE OF REVIEW: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) has made important contributions on the prevalence of and factors associated with cardiovascular disease (CVD) risk factors among diverse Hispanic/Latino adults in the US. This article summarizes the knowledge gained thus far on major CVD risk factors from this landmark study. RECENT FINDINGS: HCHS/SOL demonstrated the sizeable burdens of CVD risk in all major Hispanic/Latino groups in the US, as well as the marked variations in prevalence of hypertension, hypercholesterolemia, diabetes, obesity, and smoking by sex and background. It also identified sociodemographic, lifestyle, and sociocultural characteristics associated with risk factors. HCHS/SOL has yielded an expanding body of literature on characteristics associated with adverse CVD risk factors in this population. Long-term follow-up of this cohort will shed further light on the observed heterogeneity in CVD risk across Hispanic/Latino groups and identify specific risk/protective factors driving these variations.

Immigrant generation status and its association with pubertal timing and tempo among Hispanic girls and boys.

PURPOSE: In the United States, Hispanic-Latino children reach puberty earlier on average than non-Hispanic white children. Yet among U.S. Hispanic/Latino children, pubertal timing comparisons between immigrant generations have not been made, hence we examined whether pubertal timing differs by immigrant generational status, independent of BMI and acculturation measures. METHODS: Cross-sectional data on 724 boys and 735 girls, aged 10-15 years, from the Hispanic Community Children's Health Study/Study of Latino (SOL) Youth, were used to predict the median ages of thelarche, pubarche, and menarche in girls, and pubarche and voice change in boys, using Weibull survival models, while adjusting for SOL center, BMI, and acculturation. RESULTS: In girls, the first generation began thelarche earlier than second and third generations (median age [years] [95% confidence interval]: 7.4 [6.1, 8.8] vs. 8.5 [7.3, 9.7] and 9.1 [7.6, 10.7], respectively), but began menarche later (12.9 [12.0,137] vs. 11.8 [11.0, 12.5] and 11.6 [10.6, 12.6], respectively). Pubertal timing and tempo for boys did not differ by generational status. CONCLUSIONS: First-generation U.S. Hispanic/Latino girls had the earliest thelarche, latest menarche and longest pubertal tempo, compared to second and third generations. Factors beyond BMI and acculturation may account for the differences in pubertal timing by generational status of U.S. Hispanic/Latino girls.

Receiving hemodialysis in Hispanic ethnic dense communities is associated with better adherence and outcomes among young patients: a retrospective analysis of the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Hispanic ethnic density (HED) is a marker of better health outcomes among Hispanic patients with chronic disease. It is unclear whether community HED is associated with mortality risk among ethnically diverse patients receiving maintenance hemodialysis. METHODS: A retrospective analysis of patients in the United States cohort of the Dialysis Outcomes and Practice Patterns Study (DOPPS) database (2011-2015) was conducted (n = 4226). DOPPS data was linked to the American Community Survey database by dialysis facility zip code to obtain % Hispanic residents (HED). One way ANOVA and Kruskal Wallis tests were used to estimate the association between tertiles of HED with individual demographic, clinical and adherence characteristics, and facility and community attributes. Multivariable Cox proportional hazards models were used to estimate the mortality hazard ratio (HR) and 95% CIs by tertile of HED, stratified by age; a sandwich estimator was used to account for facility clustering. RESULTS: Patients dialyzing in facilities located in the highest HED tertile communities were younger (61.4 vs. 64.4 years), more commonly non-White (62.4% vs. 22.1%), had fewer comorbidities, longer dialysis vintage, and were more adherent to dialysis treatment, but had fewer minutes of dialysis prescribed than those in the lowest tertile. Dialyzing in the highest HED tertile was associated with lower hazard of mortality (HR, 0.86; 95% CI, 0.72-1.00), but this association attenuated with the addition of individual race/ethnicity (HR, 0.92; 95% CI, 0.78-1.09). In multivariable age-stratified analyses, those younger than 64 showed a lower hazard for mortality in the highest (vs. lowest) HED tertile (HR, 0.66; 95% CI, 0.49-0.90). Null associations were observed among patients ≥ 64 years. CONCLUSIONS: Treating in communities with greater HED and racial/ethnic integration was associated with lower mortality among younger patients which points to neighborhood context and social cohesion as potential drivers of improved survival outcomes for patients receiving hemodialysis.

Cultural and neighborhood characteristics associated with activity-specific parenting practices in Hispanic/Latino youth: a secondary analysis of the Hispanic Community Children's health study/study of Latino youth.

Hispanic/Latino youth are less physically active than non-Hispanic/Latino youth. We assessed whether activity-specific parenting practices relate to moderate-to-vigorous physical activity (MVPA) and sedentary behavior among Hispanic/Latino youth, and whether cultural (acculturation) and neighborhood characteristics (perceived barriers to activity) relate to the use of parenting practice patterns. Using the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth, n = 976 8-16-year-olds), we modeled linear regression associations between parenting practices and mean daily MVPA and sedentary behavior. Parenting practice patterns were then developed using k-means cluster analysis, and regressed on parental acculturation and neighborhood characteristics. Discipline predicted higher MVPA in females (ß 1.89 [95% CI 0.11-3.67]), while Monitoring/Reinforcement predicted higher MVPA in males (ß 4.71 [95% CI 0.68-8.74]). Three patterns were then identified: Negative Reinforcement (high Limit Setting and Discipline use), Positive Reinforcement (high Limit Setting and Monitoring/Reinforcement use), and Permissive Parenting (low parenting practice use). Higher acculturation predicted use of Positive Reinforcement. Activity-specific parenting practices are associated with activity in sex-specific ways among Hispanic/Latino youth, and cultural factors predict the use of parenting practices.

Current Family Functioning and Youth Cardiometabolic Health in the SOL Youth Study.

BACKGROUND: Family functioning may impact children's cardiometabolic health; however, few studies have examined multiple cardiometabolic markers among a diverse racial/ethnic cohort. The relationship between child- and caregiver-reported family functioning and the cardiometabolic health of Hispanic/Latino youth was examined. METHOD: Data were from the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth) (2012-2014), a population-based cohort study of children and adolescents whose parents participated in the HCHS/SOL (2008-2011). The relationship between youth- and caregiver-rated family functioning, and concordance of ratings is modeled, utilizing the general functioning subscale of the McMaster Family Assessment Device with youth objective cardiometabolic health markers (obesity, central adiposity, prediabetes/diabetes, prehypertension/hypertension, triglycerides, HDL cholesterol) adjusting for sociodemographic factors. RESULTS: Among boys, child/caregiver concordant ineffective family functioning rating was associated with higher cumulative cardiometabolic risk (adjusted B (95% CI): 0.30 (0.04, 0.56)), but no association was observed among girls (adjusted B (95% CI): 0.04 (-0.13, 0.21)). Among girls, ineffective child rating/effective caregiver rating was associated with higher cumulative cardiometabolic risk (adjusted B (95% CI): 0.27 (0.06, 0.48)), but no association was observed among boys (adjusted B (95% CI): 0.02 (-0.23, 0.27). CONCLUSION: Findings suggest that family functioning among this Hispanic/Latino population may influence cardiometabolic risk among youth. Observed differences in the associations by youth sex and concordant/discordant reports of family functioning suggest interventions at the family level, targeting both caregivers and youth, that consider differential sex effects are warranted.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.

Chronic Stress, Genetic Risk, and Obesity in US Hispanic/Latinos: Results From the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: This study aimed to investigate whether the association of chronic stress with obesity is independent of genetic risk and test whether it varies by the underlying genetic risk. METHODS: The analysis included data from the Hispanic Community Health Study/Study of Latinos, a community-based study of Hispanic/Latinos living in four US communities (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA). The sample consisted of 5336 women and 3231 men who attended the Hispanic Community Health Study/Study of Latinos second in-person examination, had measures of obesity, and chronic stress, and were genotyped. Chronic stress burden was assessed by an eight-item scale. An overall polygenic risk score was calculated based on the summary statistics from GIANT and UK BioBank meta-analysis of body mass index (BMI) genome-wide association studies. Mixed-effect models were used to account for genetic relatedness and sampling design, as well as to adjust for potential confounders. RESULTS: A higher number of chronic stressors were associated with both BMI ( ß [log odds] = 0.31 [95% confidence interval = 0.23-0.38]) and obesity ( ß [log odds] = 0.10 [95% confidence interval = 0.07-0.13]), after adjustment for covariates and genetic risk. No interactions were found between chronic stress and the genetic risk score for BMI or obesity. CONCLUSIONS: We did not find evidence for an interaction between chronic stress and polygenic risk score, which was not consistent with other publications that showed greater BMI or obesity in the groups with high stressors and elevated genetic risk.

Associations of steps per day and step intensity with the risk of diabetes: the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).

BACKGROUND: Higher levels of moderate-to-vigorous physical activity have been associated with a lower risk of diabetes, but less is known about how daily step counts (steps/day) are associated with diabetes risk. Therefore, we examined the association of steps/day and step intensity with incident diabetes. METHODS: We included 6634 adults from the population-based prospective cohort Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (2008-2017). Cox proportional hazard models that accounted for complex survey design and sampling weights were used to estimate the association of baseline accelerometer-assessed steps/day and step intensity with 6-year risk of incident diabetes as hazard ratios (HR) and 95% confidence intervals (CI). We further examined whether the percent of intense steps at a given accumulation of steps/day was associated with diabetes risk, and if associations were modified by specific cohort characteristics. RESULTS: The average age of cohort members was 39 years and 52% were female. Adults had an average of 8164 steps/day and spent 12 min/day in brisk ambulation (> 100 steps/min). Over 6 years of follow-up, there were 1115 cases of diabetes. There was a suggestive lower risk of diabetes with more steps/day- adults had a 2% lower risk per 1000 steps/day (HR = 0.98 (95% CI 0.95, 1.00)). Inverse associations between average steps/day and diabetes incidence were observed across many cohort characteristics, but most importantly among adults at high risk for diabetes - those who were older, or had obesity or prediabetes. Adults who accumulated 17 min/day in brisk ambulation compared to < 2 min/day had a 31% lower risk of diabetes (HR = 0.69 (95% CI 0.53, 0.89)). A greater percent of intense steps for a given accumulation of steps/day was associated with further risk reduction. CONCLUSION: Adults who accumulate more daily steps may have a lower risk of diabetes. Accumulating more steps/day and greater step intensity appear to be important targets for preventing diabetes.

Periodontal disease and incident prediabetes and diabetes: The Hispanic Community Health Study/Study of Latinos.

AIM: To examine whether baseline periodontal disease is independently associated with incident prediabetes and incident diabetes in Hispanics/Latinos in the United States. MATERIALS AND METHODS: This study examined 7827 individuals, 18-74 years of age without diabetes, from the Hispanic Community Health Study/Study of Latinos. Participants received a full-mouth periodontal examination at baseline (2008-2011), and the disease was classified using the Centers for Disease Control and Prevention/American Academy of Periodontology case definitions. At Visit 2 (2014-2017), incident prediabetes and diabetes were assessed using multiple standard procedures including blood tests. Multivariable survey Poisson regressions estimated the rate ratio (RR) and 95% confidence intervals (CIs) of incident prediabetes and incident diabetes associated with periodontal disease severity. RESULTS: Among the individuals without prediabetes or diabetes at baseline, 38.8% (n = 1553) had developed prediabetes and 2.2% (n = 87) had developed diabetes after 6 years. Nineteen percent (n = 727) of individuals with prediabetes at baseline developed diabetes after 6 years. Adjusting for all potential confounders, no significant association was found between periodontal disease severity and either incident prediabetes (RR: 0.93; 95% CI: 0.82-1.06) or incident diabetes (RR: 0.99; 95% CI: 0.80-1.22). CONCLUSIONS: Our findings suggest that among a diverse cohort of Hispanic/Latino individuals living in the United States, there was no association between periodontal disease severity and the development of either prediabetes or diabetes during a 6-year follow-up period.