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BackgroundTrimethylamine-N-oxide (TMAO), a diet-derived and gut microbiota-related metabolite, is associated with cardiovascular disease (CVD). However, major dietary determinants and specific gut bacterial taxa related to TMAO remain to be identified in humans.ObjectivesWe aimed to identify dietary and gut microbial factors associated with circulating TMAO.MethodsThis cross-sectional study included 3972 participants (57.3% women) aged 18-74 y from the Hispanic Community Health Study/Study of Latinos in the United States. Dietary information was collected by 24-h dietary recalls at baseline interview (2008-2011), and baseline serum TMAO and its precursors were measured by an untargeted approach. Gut microbiome was profiled by shotgun metagenomic sequencing in a subset of participants (n = 626) during a follow-up visit (2016-2018). Logistic and linear regression were used to examine associations of inverse-normalized metabolites with prevalent CVD, dietary intake, and bacterial species, respectively, after adjustment for sociodemographic, behavioral, and clinical factors.ResultsTMAO was positively associated with prevalent CVD (case number = 279; OR = 1.34; 95% CI: 1.17, 1.54, per 1-SD). Fish (P = 1.26 × 10-17), red meat (P = 3.33 × 10-16), and egg (P = 3.89 × 10-5) intakes were top dietary factors positively associated with TMAO. We identified 9 gut bacterial species significantly associated with TMAO (false discovery rate

OBJECTIVE:Hispanics/Latinos, the largest immigrant population in the USA, undergo the process of acculturation and have a large burden of heart failure risk. Few studies have examined the association of acculturation on cardiac structure and function. DESIGN:Cross-sectional. SETTING:The Echocardiographic Study of Latinos. PARTICIPANTS:1818 Hispanic adult participants with baseline echocardiographic assessment and acculturation measured by the Short Acculturation Scale, nativity, age at immigration, length of US residence, generational status and language. PRIMARY AND SECONDARY OUTCOME MEASURES:Echocardiographic assessment of left atrial volume index (LAVI), left ventricular mass index (LVMI), early diastolic transmitral inflow and mitral annular velocities. RESULTS:The study population was predominantly Spanish-speaking and foreign-born with mean residence in the US of 22.7 years, mean age of 56.4 years; 50% had hypertension, 28% had diabetes and 44% had a body mass index >30 kg/m2. Multivariable analyses demonstrated higher LAVI with increasing years of US residence. Foreign-born and first-generation participants had higher E/e' but lower LAVI and e' velocities compared with the second generation. Higher acculturation and income >$20K were associated with higher LVMI, LAVI and E/e' but lower e' velocities. Preferential Spanish-speakers with an income

Background: Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment.Results: Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA.Conclusions: Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

AimsInsulin resistance (IR) adversely impacts memory and executive functioning in non-Hispanic whites without diabetes. Less is known in Hispanics/Latinos, despite the fact that Hispanics/Latinos have higher rates of insulin resistance than non-Hispanic whites. We investigated the association between IR and cognition and its variation by age.MethodsData from 5987 participants 45-74 years old without diabetes from the Hispanic Community Health Study/Study of Latinos. IR was considered continuously using homeostasis model assessment for insulin resistance (HOMA-IR) and also dichotomized based on clinically relevant thresholds for hyperinsulinemia (fasting insulin > 84.73 pmol/L or HOMA-IR > 2.6) and sample-based norms (75th percentile of fasting insulin or HOMA-IR). Cognitive testing included the Brief Spanish English Verbal Learning Test (B-SEVLT), Verbal Fluency, and Digit Symbol Substitution.ResultsThere was 90% overlap in participant categorization comparing clinically relevant and sample-based thresholds. In separate fully-adjusted linear regression models, age modified the association between HOMA-IR and Digit Symbol Substitution (p = 0.02); advancing age combined with higher HOMA-IR levels resulted in higher scores. Age also modified the association between clinically relevant hyperinsulinemia and B-SEVLT recall (p = 0.03); with increasing age came worse performance for individuals with hyperinsulinemia.ConclusionThe relationship of IR with cognition in Hispanics/Latinos without diabetes may reflect an age- and test-dependent state.

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

Background and aimsThe Ankle-Brachial index (ABI) is a well-accepted measure of peripheral artery disease (arterial stenosis and stiffness) and has been shown to be associated with cognitive function and disorders; however, these associations have not been examined in Hispanics/Latinos. Therefore, we sought to examine relationships between ABI and cognitive function among diverse middle-age and older Hispanics/Latinos.MethodsWe used cross-sectional data on n = 7991 participants aged 45-74 years, without stroke or coronary heart disease, from the Hispanic Community Health Study/Study of Latinos. Our primary outcome, global cognition (GC), was a continuous composite score of four cognitive domains (verbal learning and memory, verbal fluency, executive function, and mental status). Secondary outcomes were the individual tests representing these domains. The ABI was analyzed continuously and categorically with standard clinical cut-points. We tested associations using generalized survey regression models incrementally adjusting for confounding factors. Age, sex, hypertension, diabetes, and dyslipidemia moderations were examined through interactions with the primary exposure.ResultsIn age, sex, and education adjusted models, continuous ABI had an inverse u-shape association with worse GC. We found similar associations with measures of verbal learning and memory, verbal fluency, executive function, but not with low mental status. The associations were attenuated, but not completely explained, by accounting for the confounders and not modified by age, sex, education, and vascular disease risks.ConclusionsIn addition to being a robust indicator of arterial compromise, our study suggests that abnormal ABI readings may also be useful for early signaling of subtle cognitive deficits.

ObjectiveThe purpose of this study is to examine the association between verbal learning, fluency, and processing speed with anxious depression symptomatology (ADS) among diverse Hispanics. We hypothesized an inverse association of anxious depression with neurocognition among Hispanics of different heritage.DesignData are from the Hispanic Community Health Study/Study of Latinos. The sample included 9,311participants aged 45-74 years (mean: 56.5 years). A latent class analysis of items from the Center for Epidemiological Studies for Depression scale and the Spielberger Trait Anxiety Inventory was used to derive an anxious depression construct. Neurocognitive measures included scores on the Brief Spanish English Verbal Learning Test (B-SEVLT, learning and recall trials), Word Fluency (WF), Digit Symbol Substitution (DSS) test, and a Global Cognitive Score (GCS). We fit survey linear regression models to test the associations between anxious depression symptomatology and cognitive function. We tested for effect modification by sex, Hispanic heritage, and age groups.ResultsAmong men, 71.6% reported low, 23.3% moderate, and 5.1% high ADS. Among women, 55.1% reported low, 33.2% moderate, and 11.8% high ADS. After controlling for age, sex, sociodemographic characteristics, cardiovascular risk factors and disease, and antidepressant use, we found significant inverse associations between moderate and high anxious depression (ref:low) with B-SEVLT learning and recall, DSS and GCS. Moderate, but not high, anxious depression was inversely associated with WF. Associations were not modified by sex, Hispanic heritage, or age.ConclusionsIncreased anxious depression symptomatology is associated with decreased neurocognitive function among Hispanics. Longitudinal studies are needed to establish temporality and infer if negative emotional symptoms precede cognitive deficits.

BackgroundFavorable levels of all readily measurable major cardiovascular disease risk factors (ie, low risk [LR]) are associated with lower risks of cardiovascular disease morbidity and mortality. Data are not available on LR prevalence among Hispanic/Latino adults of diverse ethnic backgrounds. This study aimed to describe the prevalence of a low cardiovascular disease risk profile among Hispanic/Latino adults in the United States and to examine cross-sectional associations of LR with measures of acculturation.Methods and resultsThe multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos examined 16 415 men and women aged 18 to 74 years at baseline (2008-2011) with diverse Hispanic/Latino backgrounds. Analyses involved 14 757 adults (mean age 41.3 years; 60.6% women). LR was defined using national guidelines for favorable levels of serum cholesterol, blood pressure, and body mass index and by not having diabetes mellitus and not currently smoking. Age-adjusted LR prevalence was low (8.4% overall; 5.1% for men, 11.2% for women) and varied by background (4.2% in men of Mexican heritage versus 15.0% in women of Cuban heritage). Lower acculturation (assessed using proxy measures) was significantly associated with higher odds of a LR profile among women only: Age-adjusted odds ratios of having LR were 1.64 (95% CI 1.24-2.17) for foreign-born versus US-born women and 1.96 (95% CI 1.49-2.58) for women residing in the United States

AimsTo examine among Hispanics in the U.S., a population with increased reliance on informal healthcare support structures, (1) the association between cognitive function and control of diabetes; and (2) whether this association is modified by family support.MethodsThe Digit Symbol Substitution Test (DSST), word fluency, and learning and delayed recall components of the Spanish English Verbal Learning Test were administered to 1794 Hispanic adults aged 45-76years with diagnosed diabetes. An executive function index and global cognitive function index (GCFI) were derived. Uncontrolled diabetes (HbA1c⩾7% [53mmol/mol]) was compared across quartiles of cognitive function using multivariable logit models with interaction terms for cognitive function and family support.ResultsAfter adjustment, lower DSST scores were associated with uncontrolled diabetes (P=0.03). Family support modified the relationship between other measures of cognition and diabetes control (Pinteraction: 0.002, 0.09). Among individuals with low family support, as cognitive function declined, the odds of uncontrolled diabetes increased (P-trend across quartiles of the GCFI, 0.015). Among those with low family support, persons in the lowest quartile of global cognitive function were more than twice as likely to have uncontrolled diabetes as those in the highest performing quartile (OR=2.31; 95% CI: 1.17, 4.55). There was no similar effect among those with high family support.ConclusionsFamily support may buffer the negative association between low cognitive functioning and diabetes control in US Hispanics/Latinos. Educational programs targeted at family members of middle-age and older persons with diabetes regardless of neurocognitive status may help improve population-level glycemic control.

ObjectiveSleep apnea (SA) has been linked with various forms of cardiovascular disease, but little is known about its association with peripheral artery disease (PAD) measured using the ankle-brachial index. This relationship was evaluated in the Hispanic Community Health Study/Study of Latinos.Approach and resultsWe studied 8367 Hispanic Community Health Study/Study of Latinos participants who were 45 to 74 years of age. Sleep symptoms were examined with the self-reported Sleep Health Questionnaire. SA was assessed using an in-home sleep study. Systolic blood pressure was measured in all extremities to compute the ankle-brachial index. PAD was defined as ankle-brachial index

Measurement error is a major issue in self-reported diet that can distort diet-disease relationships. Use of blood concentration biomarkers has the potential to mitigate the subjective bias inherent in self-reporting. As part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline visit (2008–2011), self-reported information on diet was collected from all participants (n  = 16,415). The HCHS/SOL also included annual telephone follow-up, as well as a second (2014–2017) and third (2020–2023) clinic visit. Blood concentration biomarkers for carotenoids, tocopherols, retinol, vitamin B12, and folate were measured in a subset of participants (n  = 476) as part of the Study of Latinos: Nutrition and Physical Activity Assessment Study (SOLNAS) (2010–2012). We examined the relationships among biomarker levels, self-reported intake, Hispanic/Latino background (Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American), and other participant characteristics in this diverse cohort. We built regression calibration–based prediction equations for 10 nutritional biomarkers and used a simulation to study the power of detecting a diet-disease association in a multivariable Cox model using a predicted concentration level. Good statistical power was observed for some nutrients with high prediction model R 2 values, but further research is needed to understand how best to realize the potential of these dietary biomarkers. This study provides a comprehensive examination of several nutritional biomarkers within the HCHS/SOL, characterizing their associations with subject characteristics and the influence of the measurement characteristics on the power to detect associations with health outcomes. [ABSTRACT FROM AUTHOR]

Our objective was to quantify the cross-sectional associations between dietary fatty acid (DFA) patterns and cognitive function among Hispanic/Latino adults. This study included data from 8942 participants of the Hispanic Community Health Study/Study of Latinos, a population-based cohort study (weighted age 56·2 years and proportion female 55·2 %). The National Cancer Institute method was used to estimate dietary intake from two 24-h recalls. We derived DFA patterns using principal component analysis with twenty-six fatty acid and total plant and animal MUFA input variables. Global cognitive function was calculated as the average z -score of four neurocognitive tests. Survey linear regression models included multiple potential confounders such as age, sex, education, depressive symptoms, physical activity, energy intake and CVD. DFA patterns were characterised by the consumption of long-chain SFA, animal-based MUFA and trans -fatty acids (factor 1); short to medium-chain SFA (factor 2); very-long-chain n -3 PUFA (factor 3); very-long-chain SFA and plant-based MUFA and PUFA (factor 4). Factor 2 was associated with greater scores for global cognitive function (β = 0·037 (sd 0·012)) and the Digit Symbol Substitution (DSS) (β = 0·56 (sd 0·17)), Brief Spanish English Verbal Learning-Sum (B-SEVLT) (β = 0·23 (sd 0·11)) and B-SEVLT-Recall (β = 0·11 (sd 0·05)) tests (P < 0·05 for all). Factors 1 (β = 0·04 (sd 0·01)) and 4 (β = 0·70 (sd 0·18)) were associated with the DSS test (P < 0·05 for all). The consumption of short to medium-chain SFA may be associated with higher cognitive function among US-residing Hispanic/Latino adults. Prospective studies are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Asthma disproportionally affects Hispanic and/or Latino backgrounds; however, the relation between circulating metabolites and asthma remains unclear. We conducted a cross-sectional study associating 640 individual serum metabolites, as well as twelve metabolite modules, with asthma in 3347 Hispanic/Latino background participants (514 asthmatics, 15.36%) from the Hispanic/Latino Community Health Study/Study of Latinos. Using survey logistic regression, per standard deviation (SD) increase in 1-arachidonoyl-GPA (20:4) was significantly associated with 32% high odds of asthma after accounting for clinical risk factors (p = 6.27 × 10−5), and per SD of the green module, constructed using weighted gene co-expression network, was suggestively associated with 25% high odds of asthma (p = 0.006). In the stratified analyses by sex and Hispanic and/or Latino backgrounds, the effect of 1-arachidonoyl-GPA (20:4) and the green module was predominantly observed in women (OR = 1.24 and 1.37, p < 0.001) and people of Cuban and Puerto-Rican backgrounds (OR = 1.25 and 1.27, p < 0.01). Mutations in Fatty Acid Desaturase 2 (FADS2) affected the levels of 1-arachidonoyl-GPA (20:4), and Mendelian Randomization analyses revealed that high genetically regulated 1-arachidonoyl-GPA (20:4) levels were associated with increased odds of asthma (p < 0.001). The findings reinforce a molecular basis for asthma etiology, and the potential causal effect of 1-arachidonoyl-GPA (20:4) on asthma provides an opportunity for future intervention. [ABSTRACT FROM AUTHOR]

Background: Both the incidence of diabetes mellitus and consumption of sugar-sweetened beverages are high in the Hispanic/Latino population in the United States. The associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers in the diverse Hispanic/Latino population in the United States are unknown.Objectives: The objective of this study was to examine the cross-sectional associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers such as fasting glucose and insulin, 2-h oral-glucose-tolerance test, HOMA-IR, HOMA index for β-cell function (HOMA-B), and glycated hemoglobin (HbA1c) among US Hispanic/Latino adults.Methods: Using baseline data from the Hispanic Community Health Study/Study of Latinos (2008-2011), beverage consumption was ascertained using two 24-h dietary recalls and a food propensity questionnaire. Diabetes/prediabetes status was defined by self-report, antihyperglycemic medication use, and American Diabetes Association laboratory criteria. Among 9965 individuals without diabetes (5194 normoglycemia, 4771 prediabetes) aged 18-74 y, the associations of beverage consumption with prediabetes and glucose metabolism markers were analyzed using logistic and linear regressions, respectively, accounting for complex survey design.Results: Compared with individuals who consumed <1 serving/d (<240 mL/d) of sugar-sweetened beverages, individuals who consumed >2 servings/d (>480 mL/d) had 1.3 times greater odds of having prediabetes (95% CI: 1.06, 1.61) and higher glucose metabolism markers including fasting glucose, fasting insulin, HOMA-IR, and HbA1c. Consumption of artificially sweetened beverages showed an inverse association with β-cell function (HOMA-B). Intake of 100% fruit juice was not significantly associated with prediabetes nor with glucose metabolism markers.Conclusions: Among US Hispanic/Latino adults, higher sugar-sweetened beverage consumption was associated with increased odds of prediabetes and higher glucose metabolism markers. Public health initiatives to decrease sugar-sweetened beverage consumption could potentially reduce the burden of diabetes among Hispanics/Latinos in the United States. [ABSTRACT FROM AUTHOR]

Inclusion of historically underrepresented populations in biomedical research is critical for large precision medicine research initiatives. Among 13,721 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) enrollees, we used multivariable-adjusted prevalence ratios to describe characteristics associated with participants' willingness to consent to different levels of biospecimen and genetic data analysis and sharing. At baseline (2008-2011), HCHS/SOL participants almost universally consented to the use of biospecimens and genetic data by study investigators and their collaborators (97.6%; 95%CI: 97.1, 98.0). Fewer consented to biospecimen and genetic data sharing with investigators not affiliated with the HCHS/SOL research team (81%, 95%CI: 80, 82) or any data sharing with commercial/for-profit entities (75%, 95%CI: 74, 76). Those refusing to share their data beyond the study investigators group were more often females, Spanish language-speakers and non-US born individuals. As expected, participants who were retained and reconsented at the six-year follow up visit tended to embrace broader data sharing, although this varied by group. Over time, Puerto Ricans and Dominicans were more likely to convert to broader data sharing than individuals of a Mexican background. Our analysis suggests that acculturation and immigration status of specific Hispanic/Latino communities may influence decisions about participation in genomic research projects and biobanks. [ABSTRACT FROM AUTHOR]

Background The association between accelerometer-assessed physical activity and risk of diabetes remains unclear, especially among US Hispanic/Latino adults who have lower levels of physical activity and a higher diabetes burden compared with other racial/ethnical populations in the country. Objectives To examine the association between accelerometer-assessed physical activity and incident diabetes in a US Hispanic/Latino population. Methods We included 7280 participants of the Hispanic Community Health Study/Study of Latinos who aged 18–74 y and free of diabetes at baseline. Data on moderate-to-vigorous physical activity (MVPA) were collected using a 7-d accelerometer measurement. Incident diabetes was assessed after a mean ± SD of 6.0 ± 0.8 y using standard procedures including blood tests. RRs and 95% CIs of diabetes associated with MVPA were estimated using survey Poisson regressions. The associations of MVPA with 6-y changes in adiposity measures were also examined. Results A total of 871 incident cases of diabetes were identified. MVPA was inversely and nonlinearly associated with risk of diabetes (P -nonlinearity = 0.006), with benefits accruing rapidly at the lower end of MVPA range (<30 min/d) and leveling off thereafter. The association differed by population age (P -interaction = 0.006). Higher MVPA was associated with lower risk of diabetes among individuals older than 50 y (RRQ4 versus Q1 = 0.50; 95% CI: 0.35, 0.73; P -trend < 0.001) but not among younger individuals (RRQ4 versus Q1 = 0.98; 95% CI: 0.66, 1.47; P -trend = 0.92). An inverse association between MVPA and 6-y gain in waist circumference was also limited to the older group (P -interaction with age < 0.001). Conclusions Among US Hispanic/Latino adults, baseline accelerometer-derived MVPA was inversely associated with incident diabetes only among individuals aged 50 y and older. Further studies are needed to confirm our findings and to clarify potential mechanisms underlying the possible age differences in the MVPA–diabetes association. This study was registered at clinicaltrials.gov as NCT02060344. [ABSTRACT FROM AUTHOR]

Background Genetic or pharmacological inhibition of de novo sphingolipid synthases prevented diabetes in animal studies. Objectives We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort. Methods We included 2010 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18–74 y who were free of diabetes and other major chronic diseases at baseline (2008–2011). Metabolomic profiling of fasting serum was performed using a global, untargeted approach. A total of 43 sphingolipids were quantified and, considering subclasses and chemical structures of individual species, 6 sphingolipid scores were constructed. Diabetes status was assessed using standard procedures including blood tests. Multivariable survey Poisson regressions were applied to estimate RR and 95% CI of incident diabetes associated with individual sphingolipids or sphingolipid scores. Results There were 224 incident cases of diabetes identified during, on average, 6 y of follow-up. After adjustment for socioeconomic and lifestyle factors, a ceramide score (RR Q4 versus Q1 = 2.40; 95% CI: 1.24, 4.65; P -trend = 0.003) and a score of sphingomyelins with fully saturated sphingoid-fatty acid pairs (RR Q4 versus Q1 = 3.15; 95% CI: 1.75, 5.67; P -trend <0.001) both were positively associated with risk of diabetes, whereas scores of glycosylceramides, lactosylceramides, or other unsaturated sphingomyelins (even if having an SFA base) were not associated with risk of diabetes. After additional adjustment for numerous traditional risk factors (especially triglycerides), both associations were attenuated and only the saturated-sphingomyelin score remained associated with risk of diabetes (RR Q4 versus Q1 = 1.98; 95% CI: 1.09, 3.59; P -trend = 0.031). Conclusions Our findings suggest that a cluster of saturated sphingomyelins may be associated with elevated risk of diabetes beyond traditional risk factors, which needs to be verified in other population studies. This study was registered at clinicaltrials.gov as NCT02060344. [ABSTRACT FROM AUTHOR]

Background: Associations of adult height with cardiometabolic and pulmonary traits have been studied in majority European ancestry populations using Mendelian randomization and polygenic risk score (PRS) analysis. The standard PRS approach entails creating a PRS for height using variants identified in prior genome-wide association studies (GWAS). It is unclear how well the standard PRS approach performs in non-European populations and whether height-trait associations observed in Europeans are also observed in other populations.Methods: In the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we used: (i) the standard approach to create a PRS for height (PRS1) and (ii) a novel approach to optimize the selection of variants from previously established height association loci to better explain height in HCHS/SOL (PRS2). We also estimated the extent to which PRS-trait associations were independent or mediated by the PRS effect on height.Results: In 7539 women and 5245 men, PRS1 and PRS2 explained 9 and 29% of the variance in measured height, respectively. Both PRS1 and PRS2 were associated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/ FVC ratio, total cholesterol and 2-hour oral glucose-tolerance test insulin levels. Additionally, PRS2 was associated with estimated glomerular filtration rate and ankle brachial index. Both PRS1 and PRS2 had pleiotropic associations with FEV1/ FVC ratio in mediation analyses.Conclusions: Associations of polygenic scores of height with measures of lung function and cholesterol were consistent with those observed in prior studies of majority European ancestry populations. Mediation analysis may augment standard PRS approaches to disentangle pleiotropic and mediated effects. [ABSTRACT FROM AUTHOR]

Background: Away-from-home foods (AFHFs) influence diet quality, a modifiable obesity risk factor, with limited generalizable evidence in Hispanic/Latino adults.Objective: We investigated associations between AFHF intake with diet quality and overweight or obesity among US Hispanic/Latino adults.Methods: Cross-sectional baseline (2008-2011) analyses included adults (n = 16,045) aged 18-74 y in the national Hispanic Community Health Study/Study of Latinos. Participants self-reported AFHF consumption frequency from 10 different settings and dietary intake (2-d 24-h recall). The Alternate Healthy Eating Index-2010 (AHEI-2010) was used to measure diet quality; higher scores indicated a healthier diet and scores were categorized into tertiles. WHO classifications categorized overweight [body mass index (BMI; kg/m2): 25.0-29.9] and obesity (BMI ≥30). Multivariate-adjusted associations of AFHF frequency or type with AHEI-2010, overweight, or obesity were assessed by using complex survey logistic regression (ORs and 95% CIs).Results: Almost half of participants (47.1%) reported eating AFHFs ≥5 times/wk. The mean ± SE AHEI-2010 score was 47.5 ± 0.2. More than one-third (37.2%) were classified as overweight and 39.6% classified as obese. Compared with consuming AFHFs ≥5 times/wk, consuming AFHFs <1 time/wk or 1-2 times/wk was associated with greater odds of being in higher AHEI-2010 tertiles, indicating a healthier diet [<1 time/wk-tertile 2: OR (95% CI): 1.6 (1.4, 1.9); tertile 3: 2.5 (2.1, 3.1); 1-2 times/wk-tertile 2: OR (95% CI): 1.4 (1.2, 1.6); tertile 3: 1.5 (1.2, 1.8)]. Consumption of AFHFs ≥1 time/wk from each AFHF setting, compared with consumption of any AFHFs <1 time/wk was associated with lower odds of being in higher AHEI-2010 tertiles. Increasing AFHF intake frequency was not associated with odds of overweight or obesity. Eating from on-street vendors ≥1 time/wk was associated with obesity (OR: 1.5; 95% CI: 1.1, 2.0).Conclusions: Consumption of AFHFs was prevalent among Hispanic/Latino adults and was associated with poorer diet quality. Findings may help to identify dietary targets to improve diet quality and prevent obesity in US Hispanics/Latinos. [ABSTRACT FROM AUTHOR]

Studies using self-reported data suggest a gene-physical activity interaction on obesity, yet the influence of sedentary behavior, distinct from a lack of physical activity, on genetic associations with obesity remains unclear. We analyzed interactions of accelerometer-measured moderate to vigorous physical activity (MVPA) and time spent sedentary with genetic variants on obesity among 9,645 U.S. Hispanics/Latinos. An overall genetic risk score (GRS), a central nervous system (CNS)-related GRS, and a non-CNS-related GRS were calculated based on 97 BMI-associated single nucleotide polymorphisms (SNPs). Genetic association with BMI was stronger in individuals with lower MVPA (first tertile) versus higher MVPA (third tertile) (β = 0.78 kg/m2 [SE, 0.10 kg/m2] vs. 0.39 kg/m2 [0.09 kg/m2] per SD increment of GRS; Pinteraction = 0.005), and in those with more time spent sedentary (third tertile) versus less time spent sedentary (first tertile) (β = 0.73 kg/m2 [SE, 0.10 kg/m2] vs. 0.44 kg/m2 [0.09 kg/m2]; Pinteraction = 0.006). Similar significant interaction patterns were observed for obesity risk, body fat mass, fat percentage, fat mass index, and waist circumference, but not for fat-free mass. The CNS-related GRS, but not the non-CNS-related GRS, showed significant interactions with MVPA and sedentary behavior, with effects on BMI and other adiposity traits. Our data suggest that both increasing physical activity and reducing sedentary behavior may attenuate genetic associations with obesity, although the independence of these interaction effects needs to be investigated further. [ABSTRACT FROM AUTHOR]

Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in U.S. Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2,499 T2D case subjects and 5,247 control subjects from six Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance levels. Conditional analysis on known index single nucleotide polymorphisms (SNPs) indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (odds ratio 1.49 [95% CI 1.27-1.75]). This association was consistent across Hispanic/Latino background groups and replicated in the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium. Among 80 previously known index SNPs at T2D loci, 66 SNPs showed consistency with the reported direction of associations and 14 SNPs significantly generalized to the HCHS/SOL. A genetic risk score based on these 80 index SNPs was significantly associated with T2D (odds ratio 1.07 [1.06-1.09] per risk allele), with a stronger effect observed in nonobese than in obese individuals. Our study identified a novel independent signal suggesting an African ancestry-specific allele at KCNQ1 for T2D. Associations between previously identified loci and T2D were generally shown in a large cohort of U.S. Hispanics/Latinos. [ABSTRACT FROM AUTHOR]

Objective: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined.Methods: Previously genome-wide association study-identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos.Results: The C-allele (frequency = 26%) of rs2943650 was significantly associated with higher BF% overall (β = 0.34 ± 0.11% per allele; P = 0.002) and in women (β = 0.41 ± 0.14% per C-allele; P = 0.003), but not in men (β = 0.28 ± 0.18% per C-allele; P = 0.11), though there was no significant sex difference. Using the inverse normal-transformed data to compare effect sizes, it was found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (β = 0.054 ± 0.018SD vs. β = 0.008 ± 0.011SD per C-allele; P = 0.03). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P < 0.05).Conclusions: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women. [ABSTRACT FROM AUTHOR]

Objective: Type 2 diabetes mellitus (DM) has been associated with lung dysfunction, but this association has not been explored in Hispanics/Latinos. The relation between diabetic nephropathy and lung function and symptoms has not been explored.Research Design and Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large, multicenter, observational study, recruited 16,415 participants aged 18-74 years (14,455 with complete data on variables of interest), between 2008 and 2011 from four U.S. communities through a two-stage area household probability design. Baseline measurements were used for analyses. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and dyspnea score were compared between individuals with and without DM, overall, and stratified by albuminuria. The analyses were performed separately for those with and without preexisting lung disease (chronic bronchitis, emphysema, asthma). Linear regression with sampling weights was used for all analyses.Results: Among Hispanics/Latinos without lung disease, those with DM had lower mean FEV1 and FVC values and a higher mean dyspnea score than those without DM (mean [95% CI] FEV1 3.00 [2.96-3.04] vs. 3.10 [3.09-3.11] L, P < 0.01; FVC 3.62 [3.59-3.66] vs. 3.81 [3.79-3.83] L, P < 0.001; dyspnea score 0.60 [0.49-0.71] vs. 0.41 [0.34-0.49], P < 0.001). Hispanics/Latinos with DM and macroalbuminuria showed 10% lower FVC (P < 0.001), 6% lower FEV1 (P < 0.001), and 2.5-fold higher dyspnea score (P = 0.04) than those without DM and with normoalbuminuria. Similar findings but with higher impairment in FVC were found in Hispanics/Latinos with lung disease.Conclusions: Hispanics/Latinos with DM have functional and symptomatic pulmonary impairment that mirror kidney microangiopathy. The progression of pulmonary impairment in adults with DM needs to be investigated further. [ABSTRACT FROM AUTHOR]

Background: Healthful diet quality has been associated with a lower risk of metabolic syndrome (MetS) in several populations, but reports on Hispanic and Latino cohorts, grouped or by ethnic background, have been limited and inconsistent.Objective: We aimed to examine diet quality by using the 2010 Alternate Healthy Eating Index [(AHEI) range: 0-110, lowest to highest quality] and its cross-sectional association with MetS and its cardiometabolic components across 6 Hispanic and Latino backgrounds.Methods: We studied 12,406 US Hispanics and Latinos, aged 18-74 y and free of diabetes, from the multicenter, population-based Hispanic Community Health Study/Study of Latinos cohort. Food and nutrients were assessed from two 24-h recalls. MetS was defined by using the 2009 harmonized guidelines. Complex survey procedures were used in multivariable-adjusted linear regression models to test the association of the AHEI with continuous markers and in logistic regression models with MetS as an outcome.Results: The prevalence of MetS was 24.2%. Overall, Hispanics and Latinos had low scores for intakes of sugar-sweetened beverages and fruit juices, whole grains, and fruit and favorable scores for trans fats and nuts and legumes, according to AHEI criteria. Adjusted mean AHEI and its individual components differed by ethnic background (P < 0.001), ranging from 43.0 for Puerto Ricans to 52.6 for Mexicans. Overall, adjusted odds (95% CIs) of having MetS were 22% (9%, 33%) lower for each 10-unit increase in AHEI. This association was modified by ethnic background (P-interaction = 0.03), with significantly lower odds observed only for Mexicans (30%; 95% CIs: 13%, 44%) and Central Americans (42%; 95% CIs: 9%, 64%) for each 10-unit increase in AHEI. AHEI was inversely associated with waist circumference, blood pressure, and glucose among Mexicans and Puerto Ricans and with triglycerides among Mexicans only, and positively associated with HDL cholesterol among Puerto Ricans and Central Americans (all P < 0.05).Conclusions: Diet quality differed by Hispanic or Latino background. Although healthier diet quality was associated with lower odds of MetS in the overall Hispanic and Latino cohort, the association of AHEI and cardiometabolic factors varied by ethnic background. Nutrition-related research and interventions among ethnically diverse groups should consider individual ethnic backgrounds to optimally address diet quality and cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT02060344. [ABSTRACT FROM AUTHOR]

The study examined the association of childhood and current economic hardship with anthropometric indices in Hispanic/Latino adults, using data from the HCHS/SOL Socio-cultural ancillary study (N = 5,084), a community-based study of Hispanic/Latinos living in four urban areas (Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA). Childhood economic hardship was defined as having experienced a period of time when one’s family had trouble paying for basic needs (e.g., food, housing), and when this economic hardship occurred: between 0–12, 13–18 years old, or throughout both of those times. Current economic hardship was defined as experiencing trouble paying for basic needs during the past 12 months. Anthropometry included height, body mass index (BMI), waist circumference (WC), and percentage body fat (%BF). Complex survey linear regression models were used to test the associations of childhood economic hardship with adult anthropometric indices, adjusting for potential confounders (e.g., age, sex, Hispanic background). Childhood economic hardship varied by Hispanic background, place of birth, and adult socio-economic status. Childhood economic hardship during both periods, childhood and adolescence, was associated with shorter height. Childhood economic hardship was associated with greater adiposity among US born individuals only. Current economic hardship was significantly associated with all three measures of adiposity (BMI, WC, %BF). These findings suggest that previous periods of childhood economic hardship appear to influence adult height more than adiposity, whereas current economic hardship may be a better determinant of adult adiposity in Hispanics. [ABSTRACT FROM AUTHOR]

Rationale: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking.Objectives: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States.Methods: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation.Measurements and Main Results: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration.Conclusions: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma. [ABSTRACT FROM AUTHOR]

Objective US Hispanics/Latinos have high prevalence of obesity and related comorbidities. We compared overall and central obesity measures in associations with cardiometabolic outcomes among US Hispanics/Latinos. Methods Multivariable regression assessed cross-sectional relationships of six obesity measures with cardiometabolic outcomes among 16,415 Hispanics/Latinos aged 18-74 years. Results BMI was moderately correlated with waist-to-hip ratio (WHR; women, r = 0.37; men, r = 0.58) and highly correlated with other obesity measures ( r ≥ 0.87) ( P < 0.0001). All measures of obesity were correlated with unfavorable levels of glycemic traits, blood pressure, and lipids, with similar r-estimates for each obesity measure ( P < 0.05). Multivariable-adjusted prevalence ratios (PRs) for diabetes (women, 6.7 [3.9, 11.5]; men, 3.9 [2.2, 6.9]), hypertension (women, 2.4 [1.9, 3.1]; men, 2.5 [1.9, 3.4]), and dyslipidemia (women, 2.1 [1.8, 2.4]; men, 2.2 [1.9, 2.6]) were highest for individuals characterized as overweight/obese (BMI ≥ 25 kg/m2) and with abnormal WHR (women ≥0.85; men, ≥0.90), compared with those with normal BMI and WHR ( P < 0.0001). Among normal-weight individuals, abnormal WHR was associated with increased cardiometabolic condition prevalence ( P < 0.05), particularly diabetes (women, PR = 4.0 [2.2, 7.1]; men, PR = 3.0 [1.6, 5.7]). Conclusions Obesity measures were associated with cardiometabolic risk factors to a similar degree in US Hispanics/Latinos. WHR is useful to identify individuals with normal BMI at increased cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Background: Whether physical activity can reduce cardiometabolic risk particularly in understudied populations such as US Hispanics/Latinos is of public health interest. We prospectively examined the association of physical activity and cardiometabolic biomarkers in n = 8049 participants of the Hispanic Community Health Study/Study of Latinos, a community-based cohort study of 16,415 adults aged 18-74 yr who self-identified as Hispanic/Latino from four US urban centers.Methods: We assessed physical activity using accelerometry in 2008-2011 at visit 1. We assessed cardiometabolic biomarkers twice: once at visit 1 and collected a second measure in 2014-2017 at visit 2. We used survey linear regression models with changes in cardiometabolic markers as the dependent variables and quartiles of sedentary behavior or whether adults met guidelines for moderate-to-vigorous physical activity as the independent variables.Results: In normoglycemic adults without cardiovascular disease, but not in adults with evidence of cardiometabolic disease, those who were in the lowest quartile for sedentary behavior (< 10.08 h/day) had a significant decline in mean LDL-cholesterol of - 3.94 mg/dL (95% CI: - 6.37, - 1.52) compared to adults in the highest quartile (≥13.0 h/day) who exhibited a significant increase in LDL-cholesterol of 0.14 mg/dL (95% CI, - 2.15,2.42) over the six year period (P < 0.02 in fully adjusted models.) There was also a trend toward lower mean increase in HbA1c comparing the lowest with the highest quartile of sedentary behavior. Overall regardless of glycemic level or evidence of cardiometabolic disease, adults who met guidelines for moderate-to-vigorous physical activity at visit 1, had significantly lower mean increases in level of fasting glucose compared to adults not meeting guidelines in fully adjusted models.Conclusions: In this cohort of Hispanics/Latinos, being free of cardiometabolic disease and having low levels of sedentary behavior were associated with health benefits. Among all adults regardless of cardiometabolic disease, meeting guidelines for moderate-to-vigorous physical activity was associated with health benefits. Overall these data suggest that an active lifestyle may blunt the association of advancing age with worsening cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

Background: Excessive sedentary time is ubiquitous in developed nations and is associated with deleterious health outcomes. Few studies have examined whether the manner in which sedentary time is accrued (in short or long bouts) carries any clinical relevance. The purpose of this study was to examine the association of prolonged, uninterrupted sedentary behavior with glycemic biomarkers in a cohort of US Hispanic/Latino adults.Methods: We studied 12 083 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a population-based study of Hispanic/Latino adults 18 to 74 years of age. Homeostatic model assessment of insulin resistance and glycosylated hemoglobin were measured from a fasting blood sample, and 2-hour glucose was measured after an oral glucose tolerance test. Sedentary time was objectively measured with a hip-mounted accelerometer. Prolonged, uninterrupted sedentariness was expressed as mean sedentary bout length.Results: After adjustment for potential confounders and moderate to vigorous physical activity, longer sedentary bout duration was dose-dependently associated with increased homeostatic model assessment of insulin resistance (P for trend<0.001) and 2-hour glucose levels (P for trend=0.015). These associations were not independent of total sedentary time; however, a significant interaction between sedentary bout duration and total sedentary time was observed. Evaluation of the joint association of total sedentary time and sedentary bout duration showed that participants in the upper quartile for both sedentary characteristics (ie, high total sedentary time and high sedentary bout duration) had the highest levels of homeostatic model assessment of insulin resistance (P<0.001 versus low group for both sedentary characteristics) and 2-hour glucose (P=0.002 versus low group for both sedentary characteristics). High total sedentary time or high sedentary bout duration alone were not associated with differences in any glycemic biomarkers.Conclusions: Accruing sedentary time in prolonged, uninterrupted bouts may be deleteriously associated with biomarkers of glucose regulation. [ABSTRACT FROM AUTHOR]

We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ancestry-specific PCA, we found significant population structure within African, European, and Amerindian ancestries in the Hispanic/Latino individuals in our study. In the African ancestral component of the admixed individuals, individuals whose grandparents were from Central America clustered separately from individuals whose grandparents were from the Caribbean, and also from reference Yoruba and Mandenka West African individuals. In the European component, individuals whose grandparents were from Puerto Rico diverged partially from other background groups. In the Amerindian ancestral component, individuals clustered into multiple different groups depending on the grandparental country of origin. Therefore, local ancestry estimation provides further insight into the complex genetic structure of US Hispanic/Latino populations, which must be properly accounted for in genotype-phenotype association studies. It also provides a basis for admixture mapping and ancestry-specific allele frequency estimation, which are useful in the identification of risk factors for disease. [ABSTRACT FROM AUTHOR]

Background: Sedentary behavior is recognized as a distinct construct from lack of moderate-vigorous physical activity and is associated with deleterious health outcomes. Previous studies have primarily relied on self-reported data, whereas data on the relationship between objectively measured sedentary time and cardiometabolic biomarkers are sparse, especially among US Hispanics/Latinos.Methods and Results: We examined associations of objectively measured sedentary time (via Actical accelerometers for 7 days) and multiple cardiometabolic biomarkers among 12 083 participants, aged 18 to 74 years, from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos of diverse backgrounds (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) were recruited from 4 US cities between 2008 and 2011. Sedentary time (<100 counts/min) was standardized to 16 hours/d of wear time. The mean sedentary time was 11.9 hours/d (74% of accelerometer wear time). After adjustment for moderate-vigorous physical activity and confounding variables, prolonged sedentary time was associated with decreased high-density lipoprotein cholesterol (P=0.04), and increased triglycerides, 2-hour glucose, fasting insulin, and homeostatic model assessment of insulin resistance (all P<0.0001). These associations were generally consistent across age, sex, Hispanic/Latino backgrounds, and physical activity levels. Even among individuals meeting physical activity guidelines, sedentary time was detrimentally associated with several cardiometabolic biomarkers (diastolic blood pressure, high-density lipoprotein cholesterol, fasting and 2-hour glucose, fasting insulin and homeostatic model assessment of insulin resistance; all P<0.05).Conclusions: Our large population-based, objectively derived data showed deleterious associations between sedentary time and cardiometabolic biomarkers, independent of physical activity, in US Hispanics/Latinos. Our findings emphasize the importance of reducing sedentary behavior for the prevention of cardiometabolic diseases, even in those who meet physical activity recommendations. [ABSTRACT FROM AUTHOR]