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Abstract Background Left ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD. Results We included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion involving tissue Doppler assessment and left atrial volume index measurements. Among 1996 participants, 916 (45.9%) had prevalent LVDD, and 212 out of 594 participants without LVDD at baseline developed incident LVDD over a median 4.3 years of follow-up. Using multivariable-adjusted analysis of compositions of microbiomes (ANCOM-II) method, we identified 7 out of 512 dominant gut bacterial species (prevalence > 20%) associated with prevalent LVDD (FDR-q < 0.1), with inverse associations being found for Intestinimonas_massiliensis, Clostridium_phoceensis, and Bacteroide_coprocola and positive associations for Gardnerella_vaginali, Acidaminococcus_fermentans, Pseudomonas_aeruginosa, and Necropsobacter_massiliensis. Using multivariable adjusted linear regression, 220 out of 669 circulating metabolites with detection rate > 75% were associated with the identified LVDD-related bacterial species (FDR-q < 0.1), with the majority being linked to Intestinimonas_massiliensis, Clostridium_phoceensis, and Acidaminococcus_fermentans. Furthermore, 46 of these bacteria-associated metabolites, mostly glycerophospholipids, secondary bile acids, and amino acids, were associated with prevalent LVDD (FDR-q < 0.1), 21 of which were associated with incident LVDD (relative risk ranging from 0.81 [p = 0.001, for guanidinoacetate] to 1.25 [p = 9 × 10−5, for 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)]). The inclusion of these 21 bacterial-related metabolites significantly improved the prediction of incident LVDD compared with a traditional risk factor model (the area under the receiver operating characteristic curve [AUC] = 0.73 vs 0.70, p = 0.001). Metabolite-based proxy association analyses revealed the inverse associations of Intestinimonas_massilliensis and Clostridium_phoceensis and the positive association of Acidaminococcus_fermentans with incident LVDD. Conclusion In this study of US Hispanics/Latinos, we identified multiple gut bacteria and related metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity. Video Abstract

Abstract Sleep-disordered breathing (SDB) is a prevalent disorder characterized by recurrent episodic upper airway obstruction. Using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we apply principal component analysis (PCA) to seven SDB-related measures. We estimate the associations of the top two SDB PCs with serum levels of 617 metabolites, in both single-metabolite analysis, and a joint penalized regression analysis. The discovery analysis includes 3299 individuals, with validation in a separate dataset of 1522 individuals. Five metabolite associations with SDB PCs are discovered and replicated. SDB PC1, characterized by frequent respiratory events common in older and male adults, is associated with pregnanolone and progesterone-related sulfated metabolites. SDB PC2, characterized by short respiratory event length and self-reported restless sleep, enriched in young adults, is associated with sphingomyelins. Metabolite risk scores (MRSs), representing metabolite signatures associated with the two SDB PCs, are associated with 6-year incident hypertension and diabetes. These MRSs have the potential to serve as biomarkers for SDB, guiding risk stratification and treatment decisions.

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

BackgroundCardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals.MethodsParticipants included 1,886 Hispanic/Latino adults (50–85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos—Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (

Abstract Introduction We investigated cognitive profiles among diverse, middle‐aged and older Hispanic/Latino adults in the Study of Latinos–Investigation of Neurocognitive Aging (SOL‐INCA) cohort using a cross‐sectional observational study design. Methods Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL‐INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function. Results Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average‐to‐high‐average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average‐to‐low‐average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low‐average‐to‐mildly impaired across all cognitive/IADL tests (12.1%). Discussion Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community‐dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos. Highlights The present study characterized cognitive profiles among diverse middle‐aged and older Hispanic/Latino adults. Latent profile analysis of neurocognitive test scores was the primary analysis conducted. The target population consists of middle‐aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos ‐ Investigation of Neurocognitive Aging.

Background and Purpose Social determinants of health (SDOH) are non-medical factors that may contribute to the development of diseases, with a higher representation in underserved populations. Our objective is to determine the association of unfavorable SDOH with self-reported stroke/transient ischemic attack (TIA) and vascular risk factors (VRFs) among Hispanic/Latino adults living in the US. Methods We used cross-sectional data from the Hispanic Community Health Study/Study of Latinos. SDOH and VRFs were assessed using questionnaires and validated scales and measurements. We investigated the association between the SDOH (individually and as count: ≤1, 2, 3, 4, or ≥5 SDOH), VRFs and stroke/TIA using regression analyses. Results For individuals with stroke/TIA (n=388), the mean age (58.9 years) differed from those without stroke/TIA (n=11,210; 46.8 years; P

Summary: Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

Summary: Background: The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA. Findings: Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids. Interpretation: We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation. Funding: Described in methods.

Seed orientation is an important factor in high-speed automatic seeders used for sowing crops such as garlic cloves and corn kernels. However, obtaining accurate seed orientation angles can be challenging due to high-frequency noise points and false top features in seed images, which can negatively impact the orientation effect. In this paper, we introduce a directional adjustment method based on the polar radius distribution map to address this issue. Our method involves two main steps. Firstly, we use the morphological opening operation to process speckles and some seed apex parts and use the region marker to obtain the original polar radius distribution curve signal. Secondly, we use the wavelet packet transform to analyze the original polar radius distribution curve signal, which yields a direction rotation angle after analysis and calculation and enables the determination of seed orientation. Our experimental results show that our method can better identify the germination location at the top of the seed, and the calculated rotation angle is more conducive to seed direction adjustment than the rotation angle directly determined by the maximum polar radius in the polar radius vector. This is due to the advantage of higher frequency resolution of wavelet packet analysis, which enables us to obtain a polar radius distribution curve signal with low noise, better smoothness, and more realistic reflection of the edge characteristics of the seed contour boundary. The proposed method provides an effective solution for accurately adjusting the orientation of garlic cloves and corn kernels and potentially other crops that require automation technology. Our key finding is that using the polar radius distribution map and wavelet packet transform can yield better results in seed orientation adjustment, by removing high-frequency noise points and false top features and improving the accuracy of seed rotation angle calculation.

ABSTRACTBackground The gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities, but population-based studies of the gut microbiome across a wide range of kidney function and damage are lacking.Methods In the Hispanic Community Health Study/Study of Latinos, gut microbiome was assessed by shotgun sequencing of stool (n = 2,438; 292 with suspected CKD). We examined cross-sectional associations of estimated glomerular filtration rate (eGFR), urinary albumin:creatinine (UAC) ratio, and CKD with gut microbiome features. Kidney trait-related microbiome features were interrogated for correlation with serum metabolites (n = 700), and associations of microbiome-related serum metabolites with kidney trait progression were examined in a prospective analysis (n = 3,635).Results Higher eGFR was associated with overall gut microbiome composition, greater abundance of species from Prevotella, Faecalibacterium, Roseburia, and Eubacterium, and microbial functions related to synthesis of long-chain fatty acids and carbamoyl-phosphate. Higher UAC ratio and CKD were related to lower gut microbiome diversity and altered overall microbiome composition only in participants without diabetes. Microbiome features related to better kidney health were associated with many serum metabolites (e.g., higher indolepropionate, beta-cryptoxanthin; lower imidazole propionate, deoxycholic acids, p-cresol glucuronide). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in UAC ratio over ~6 y.Conclusions Kidney function is a significant correlate of the gut microbiome, while the relationship of kidney damage with the gut microbiome depends on diabetes status. Gut microbiome metabolites may contribute to CKD progression.

Abstract Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE- $$\epsilon 2$$ ϵ 2 and APOE- $$\epsilon 4$$ ϵ 4 alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE- $$\epsilon 4$$ ϵ 4 and APOE- $$\epsilon 2$$ ϵ 2 alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE- $$\epsilon 4$$ ϵ 4 and APOE- $$\epsilon 2$$ ϵ 2 alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults.

Abstract Background Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. Methods We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. Results By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. Conclusions Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.

Abstract Applying causal inference methods, such as weighting and matching methods, to a survey sampled population requires properly incorporating the survey weights and design to obtain effect estimates that are representative of the target population and correct standard errors (SEs). With a simulation study, we compared various approaches for incorporating the survey weights and design into weighting and matching-based causal inference methods. When the models were correctly specified, most approaches performed well. However, when a variable was treated as an unmeasured confounder and the survey weights were constructed to depend on this variable, only the matching methods that used the survey weights in causal estimation and as a covariate in matching continued to perform well. If unmeasured confounders are potentially associated with the survey sample design, we recommend that investigators include the survey weights as a covariate in matching, in addition to incorporating them in causal effect estimation. Finally, we applied the various approaches to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and found that insomnia has a causal association with both mild cognitive impairment (MCI) and incident hypertension 6–7 years later in the US Hispanic/Latino population.

Abstract APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) population and African Americans from the Atherosclerosis Risk In Communities (ARIC) study. We identified 5 Amerindian and 14 African enriched variants with an expected moderate effect. A suggestive significant interaction (p-value = 0.01) was found for one African-enriched variant, rs8112679, located in the ZNF222 gene fourth exon. Our results suggest there are no ancestry-enriched variants with large effect sizes of interaction effects with APOE-ɛ4 on MCI in the APOE region in the Hispanic/Latino population. Further studies are needed in larger datasets to identify potential interactions with smaller effect sizes.

Background There is limited evidence on the potential negative metabolic health impacts of prolonged and uninterrupted sedentary bouts in structurally disadvantaged youth. This study investigated associations between sedentary bout variables and metabolic health markers in the Hispanic Community Health Study/SOL Youth (Study of Latino Youth). Methods and Results SOL Youth was a population‐based cohort of 1466 youth (age range, 8–16 years; 48.5% female); 957 youth were included in the analytic sample based on complete data. Accelerometers measured moderate‐to‐vigorous physical activity (MVPA), total sedentary time, and sedentary bout patterns (daily time spent in sedentary bouts ≥30 minutes, median sedentary bout duration, and number of daily breaks from sedentary time). Clinical measures included body mass index, waist circumference, fasting glucose, glycated hemoglobin, fasting insulin, and the homeostasis model assessment of insulin resistance. After adjusting for sociodemographics, total sedentary time, and MVPA, longer median bout durations and fewer sedentary breaks were associated with a greater body mass index percentile (bbouts=0.09 and bbreaks=−0.18), waist circumference (bbouts=0.12 and bbreaks=−0.20), and fasting insulin (bbouts=0.09 and bbreaks=−0.21). Fewer breaks were also associated with a greater homeostasis model assessment of insulin resistance (b=−0.21). More time in bouts lasting ≥30 minutes was associated with a greater fasting glucose (b=0.18) and glycated hemoglobin (b=0.19). Conclusions Greater accumulation of sedentary time in prolonged and uninterrupted bouts had adverse associations with adiposity and glycemic control over and above total sedentary time and MVPA. Findings suggest interventions in Hispanic/Latino youth targeting both ends of the activity spectrum (more MVPA and less prolonged/uninterrupted sedentary patterns) may provide greater health benefits than those targeting only MVPA.

An integrated multi-omics analysis identifies an association chain among sleep-disordered breathing (SDB) traits, gene expression in circulating leukocytes, and serum metabolites, and supports a mechanistic role for P2XR4 purinergic signaling in SDB.

Abstract Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of upper airway obstruction during sleep resulting in oxygen desaturation and sleep fragmentation, and associated with increased risk of adverse health outcomes. Metabolites are being increasingly used for biomarker discovery and evaluation of disease processes and progression. Studying metabolomic associations with OSA in a diverse community-based cohort may provide insights into the pathophysiology of OSA. We aimed to develop and replicate a metabolite index for OSA and identify individual metabolites associated with OSA. We studied 219 metabolites and their associations with the apnea hypopnea index (AHI) and with moderate-severe OSA (AHI ≥ 15) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n = 3507) using two methods: (1) association analysis of individual metabolites, and (2) least absolute shrinkage and selection operator (LASSO) regression to identify a subset of metabolites jointly associated with OSA, which was used to develop a metabolite index for OSA. Results were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 475). When assessing the associations with individual metabolites, we identified seven metabolites significantly positively associated with OSA in HCHS/SOL (FDR p

Summary: Estimated glomerular filtration rate (eGFR) is used to evaluate kidney function and determine the presence of chronic kidney disease (CKD), a highly prevalent disease in the US1,2,3 that varies among subgroups of Hispanic/Latino individuals.4,5 The polygenic risk score (PRS) is a popular method that uses large genome-wide association studies (GWASs) to provide a strong estimate of disease risk.7 However, due to the limited availability of summary statistics from GWAS meta-analyses based on Hispanic/Latino populations, PRSs can only be computed using different ancestry GWASs. The performance of eGFR PRSs derived from other GWAS reference populations for Hispanic/Latino population has not been examined. We compared PRS constructions for eGFR prediction in Hispanic/Latino individuals using GWAS-significant variants, clumping and thresholding (C&T),8 and PRS-CS,22 as well as a combination of PRSs calculated with different reference GWAS meta-analyses from European and multi-ethnic studies in Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). All eGFR PRSs were highly associated with eGFR (p

A misdiagnosis of pulmonary embolism (PE) can have severe consequences such as disability or death. It's crucial to accurately identify key clinical features of PE in clinical practice to promptly identify potential PE patients who may present asymptomatically, and to prevent misdiagnosing PE as asthma exacerbation in patients with symptoms like dyspnea or chest pain. However, reliably identifying these important features can be challenging due to many factors influencing the likelihood of PE development in complex fashions (e.g., the interactions among these factors). To address this difficulty, we presented an effective framework using the deep neural network (DNN) model and the permutation-based feature importance test (PermFIT) procedure, i.e., PermFIT-DNN. We applied the PermFIT-DNN framework to the analysis of data from a PE study for asthma exacerbation patients. Our analysis results show that the PermFIT-DNN framework can robustly identify key features for classifying PE status. The important features identified can also aid in accurately predicting the PE risk.

Summary: We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants’ level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person’s health on a 1 (not at all useful) to 10 (extremely useful) scale. There were 5,769 HCHS/SOL participants who completed at least one survey question. Of the target population, 55.2% was aware of at least one type of genetic test. Awareness varied between HCHS/SOL enrollment sites and was higher among individuals who had higher educational attainment and had higher incomes. Only 3.3% of the target population reported receiving one or more of the tests described. HCHS/SOL individuals rated the usefulness as 8.4, on average, with lower scores observed among U.S.-born individuals compared to individuals born outside the United States, with differences by HCHS/SOL enrollment sites. In conclusion, while awareness of genetic testing among Hispanic and Latino individuals varies by location, education, and income, perceptions about its usefulness are high while experiences with testing are rare. Results identify groups and locations that may benefit from greater outreach about the capabilities of genetic testing and precision medicine.

Traditional case–control genetic association studies examine relationships between case–control status and one or more covariates. It is becoming increasingly common to study secondary phenotypes and their association with the original covariates. The Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project, a study of temporomandibular disorders (TMD), motivates this work. Numerous measures of interest are collected at enrollment, such as the number of comorbid pain conditions from which a participant suffers. Examining the potential genetic basis of these measures is of secondary interest. Assessing these associations is statistically challenging, as participants do not form a random sample from the population of interest. Standard methods may be biased and lack coverage and power. We propose a general method for the analysis of arbitrary phenotypes utilizing inverse probability weighting and bootstrapping for standard error estimation. The method may be applied to the complicated association tests used in next-generation sequencing studies, such as analyses of haplotypes with ambiguous phase. Simulation studies show that our method performs as well as competing methods when they are applicable and yield promising results for outcome types, such as time-to-event, to which other methods may not apply. The method is applied to the OPPERA baseline case–control genetic study.

Abstract Background Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos. Results The fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia, Prevotella, Dorea, and Coprococcus. In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus. Conclusions Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.

Abstract Background Previous studies have shown an association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), but it is unclear whether the association is independent of metabolic syndrome. Methods Data from 13,006 participants aged 18 to 74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) without viral hepatitis, excessive alcohol consumption, or high transferrin saturation levels were analyzed. Suspected NAFLD was defined as presence of sex-specific elevations in serum aminotransferase levels (aspartate aminotransferase (AST) > 37 U/L or alanine aminotransferase (ALT) > 40 U/L for men and AST or ALT > 31 U/L for women). Logistic regression was used to examine cross-sectional associations of elevated serum aminotransferase levels with low estimated glomerular filtration rate (eGFR 17 mg/g in men and > 25 mg/ g in women) in separate models adjusting for demographic characteristics and metabolic syndrome. Results Mean (SD) age was 41 (0.27) years, and 45 % were male. Elevated serum aminotransferase levels were noted in 18.8 % of the population and were associated with greater odds of high UACR (OR = 1.31; 95 % CI = 1.10, 1.56) after adjusting for demographic characteristics; this association became non-significant after adjustment for metabolic syndrome (OR = 1.11, 95 % CI = 0.92, 1.33). In contrast, elevated serum aminotransferase levels were not associated with low eGFR (odds ratio (OR) = 0.73; 95 % confidence interval (CI) = 0.45, 1.18) after adjusting for covariates. Conclusions In this sample of diverse U.S. Hispanic Latino adults, elevated serum aminotransferase levels were not independently associated with measures of CKD.

Summary: Background: Obstructive Sleep Apnoea (OSA) often co-occurs with cardiometabolic and pulmonary diseases. This study is to apply genetic analysis methods to explain the associations between OSA and related phenotypes. Methods: In the Hispanic Community Healthy Study/Study of Latinos, we estimated genetic correlations ρg between the respiratory event index (REI) and 54 anthropometric, glycemic, cardiometabolic, and pulmonary phenotypes. We used summary statistics from published genome-wide association studies to construct Polygenic Risk Scores (PRSs) representing the genetic basis of each correlated phenotype (ρg>0.2 and p-value

ABSTRACT Menopause is a pivotal period during which loss of ovarian hormones increases cardiometabolic risk and may also influence the gut microbiome. However, the menopause-microbiome relationship has not been examined in a large study, and its implications for cardiometabolic disease are unknown. In the Hispanic Community Health Study/Study of Latinos, a population with high burden of cardiometabolic risk factors, shotgun metagenomic sequencing was performed on stool from 2,300 participants (295 premenopausal women, 1,027 postmenopausal women, and 978 men), and serum metabolomics was available on a subset. Postmenopausal women trended toward lower gut microbiome diversity and altered overall composition compared to premenopausal women, while differing less from men, in models adjusted for age and other demographic/behavioral covariates. Differentially abundant taxa for post- versus premenopausal women included Bacteroides sp. strain Ga6A1, Prevotella marshii, and Sutterella wadsworthensis (enriched in postmenopause) and Escherichia coli-Shigella spp., Oscillibacter sp. strain KLE1745, Akkermansia muciniphila, Clostridium lactatifermentans, Parabacteroides johnsonii, and Veillonella seminalis (depleted in postmenopause); these taxa similarly differed between men and women. Postmenopausal women had higher abundance of the microbial sulfate transport system and decreased abundance of microbial β-glucuronidase; these functions correlated with serum progestin metabolites, suggesting involvement of postmenopausal gut microbes in sex hormone retention. In postmenopausal women, menopause-related microbiome alterations were associated with adverse cardiometabolic profiles. In summary, in a large U.S. Hispanic/Latino population, menopause is associated with a gut microbiome more similar to that of men, perhaps related to the common condition of a low estrogen/progesterone state. Future work should examine similarity of results in other racial/ethnic groups. IMPORTANCE The menopausal transition, marked by declining ovarian hormones, is recognized as a pivotal period of cardiometabolic risk. Gut microbiota metabolically interact with sex hormones, but large population studies associating menopause with the gut microbiome are lacking. Our results from a large study of Hispanic/Latino women and men suggest that the postmenopausal gut microbiome in women is slightly more similar to the gut microbiome in men and that menopause depletes specific gut pathogens and decreases the hormone-related metabolic potential of the gut microbiome. At the same time, gut microbes may participate in sex hormone reactivation and retention in postmenopausal women. Menopause-related gut microbiome changes were associated with adverse cardiometabolic risk in postmenopausal women, indicating that the gut microbiome contributes to changes in cardiometabolic health during menopause.

In this study, a comprehensive treatment process based on the rotary injection of Ar+CO2 Mg-Al alloy melt is proposed. The effect of carbon on the grain refinement of Mg-Al alloy is studied according to the proposed integrated treatment process. The regularity of carbon refinement in the Mg-Al alloy is examined by microstructural observation and theoretical calculation. The results show that carbon has no effect on the grain refinement of Mg-Al alloy when the Al content is less than 1wt.%. However, when the Al content reaches 2 wt.%, the refining effect is obvious, and the grain refinement efficiency is 62%. The refining effect increases with the increase in the Al content, and the refinement efficiency becomes 79% when the Al content reaches 9 wt.%. The size of Al-C-O in the matrix is approximately 5μm, which confirms the existence of Al4C3 phase exists as a heterogeneous nucleating agent. The theoretical calculations suggest that the Al4C3 heterogeneous nucleating agent cannot be formed when the Al content in the Mg alloy is less than 1.34%, so there is no thinning effect under such Al content. The crystallographic calculations reveal that the mismatch between the Al4C3 phase and Mg alloy matrix is only 4.05%, and Al4C3 can exist as a heterogeneous nucleating agent for α-Mg phase. Combining the measured solidification curves with the classical nucleation theory, the wetting angle of Mg-Al alloy on Al4C3 is calculated to be 24.3°.

Introduction: Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We examined the role of gene–environment interactions to better characterize the sociocultural environmental determinants and their genome-scale interactions, which may contribute to missing heritability of obesity. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).Methods: PRSs were derived using genome-wide association study (GWAS) weights from a publicly available, large meta-analysis of European ancestry samples. Generalized linear models were run using a set of a priori acculturation-related and environmental factors measured at visit 1 (2008–2011) and visit 2 (2014–2016) in an analytic subsample of 8,109 unrelated individuals with genotypic, phenotypic, and complete case data at both visits. We evaluated continuous measures of BMI and waist-to-hip ratio. All models were weighted for complex sampling design, combined, and sex-stratified.Results: Overall, we observed a consistent increase of BMI with greater PRS across both visits. We found the best-fitting model adjusted for top five principal components of ancestry, sex, age, study site, Hispanic/Latino background genetic ancestry group, sociocultural factors and PRS interactions with age at immigration, years since first arrival to the United States (p < 0.0104), and healthy diet (p < 0.0036) and explained 16% of the variation in BMI. For every 1-SD increase in PRS, there was a corresponding 1.10 kg/m2 increase in BMI (p < 0.001). When these results were stratified by sex, we observed that this 1-SD effect of PRS on BMI was greater for women than men (1.45 vs. 0.79 kg/m2, p < 0.001).Discussion: We observe that age at immigration and the adoption of certain dietary patterns may play a significant role in modifying the effect of genetic risk on obesity. Careful consideration of sociocultural and immigration-related factors should be evaluated. The role of nongenetic factors, including the social environment, should not be overlooked when describing the performance of PRS or for promoting population health in understudied populations in genomics.

Objective: Examine cross-sectional and longitudinal associations of accelerometer measured step volume (steps/day) and cadence with adiposity and six-year changes in adiposity in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: HCHS/SOL’s target population was 60% female with a mean age of 41 years. Cross-sectional (n = 12,353) and longitudinal analyses (n = 9,077) leveraged adjusted complex survey regression models to examine associations between steps/day, and cadence with weight (kg), waist circumference (cm) and body mass index (kg/m2). Effect measure modification by covariates was examined. Results: Lower steps/day and intensity was associated with higher adiposity at baseline. Compared to those in the highest quartile of steps/day those in the lowest quartile have 1.42 95% CI (1.19, 1.70) times the odds of obesity. Compared to those in the highest categories of cadence step-based metrics, those in the lowest categories had a 1.62 95% CI (1.36, 1.93), 2.12 95% CI (1.63, 2.75) and 1.41 95% CI (1.16, 1.70) odds of obesity for peak 30-minute cadence, brisk walking and faster ambulation and bouts of purposeful steps and faster ambulation, respectively. Compared to those with the highest stepping cadences, those with the slowest peak 30-minute cadence and fewest minutes in bouts of purposeful steps and faster ambulation had 0.72 95% CI (0.57, 0.89) and 0.82 95% CI (0.60, 1.14) times the odds of gaining weight, respectively. Conclusion: Inverse cross-sectional relationships were found for steps/day and cadence and adiposity. Over a six-year period, higher step intensity but not volume was associated with higher odds of gaining weight.

Background Evidence suggests that subjective (perceived) social status (SSS) may predict health outcomes more strongly than objective social status, but little is known about the relationship between SSS and cardiovascular health (CVH). This study focuses on this relationship among diverse Hispanic/Latino adults because while poor CVH profiles are prevalent in this population, immigration complicates attempts to measure their social status. Methods and Results We analyzed baseline HCHS/SOL (Hispanic Community Health Study/Study of Latinos) data on 15 374 Hispanic/Latino adults aged 18 to 74 years in 2008 to 2011. SSS was assessed using the McArthur Scale, a 10‐rung “social ladder.” CVH was based on levels of 7 metrics defined by the American Heart Association. Linear and logistic regressions were used to examine cross‐sectional associations of SSS with CVH (overall and single metrics) after adjusting for objective social status, demographic, and health factors. Less than half of the population (46%) had Ideal scores in ≥4 metrics of CVH. In multivariable‐adjusted models, an increase in SSS was associated with a higher overall CVH score (β=0.04; 95% CI, 0.01–0.06) and greater likelihood of Ideal levels of body mass index, physical activity, and fasting blood glucose levels. Nativity and time in the United States modified the association between SSS and Ideal smoking. Conclusions Subjective measures of social status can enhance an understanding of CVH among Hispanic/Latino people. Future studies should explore the stability of SSS over time in comparison with objective social status and the mechanisms through which SSS may influence CVH.

Abstract Individuals of South Asian ethnicity have an increased risk for obesity and related diseases. Foods available in the home during the first 1000 days (conception to 24 months old) are an important determinant of diet, yet no study has examined the association of early‐life home food availability (HFA) with later diet and obesity risk in South Asian households. We examined whether obesogenic HFA at 18 months of age is associated with dietary intake and body mass index (BMI) at 36 months of age in low‐income Pakistani and White households in the United Kingdom. In this prospective birth cohort study (Born in Bradford 1000), follow‐up assessments occurred at 18 (n = 1032) and 36 (n = 986) months of age. Variety and quantity of snack foods and sugar‐sweetened beverages (SSBs) in the home and consumed were measured using the HFA Inventory Checklist and food frequency questionnaires, respectively. BMI was calculated using measured length/height and weight. Multinomial logistic regression models examined associations between HFA and tertiles of dietary intake, and multivariable linear regression models assessed associations between HFA and BMI. Pakistani households had a greater variety and quantity of snack foods and SSBs available compared with White households. Variety and quantity of snack foods and SSBs in the home at 18 months were positively associated with children's intake of these items at 36 months, but associations between HFA and BMI were null. Reducing obesogenic HFA during the first 1000 days may promote the development of more healthful diets, though this may not be associated with lower obesity risk during toddlerhood.

Rationale & Objective: Recent studies suggest that periodontal disease may be associated with incident chronic kidney disease (CKD). However, studies have focused on older populations, and US Hispanics/Latinos were not well represented. Study Design: Observational cohort. Setting & Participants: We analyzed data from the Hispanic Community Health Study/Study of Latinos who completed a baseline visit with a periodontal examination and a follow-up visit, and did not have CKD at baseline. Predictors: Predictors included ≥30% of sites with clinical attachment loss ≥3 mm, ≥30% of sites with probing depth ≥4 mm, percentage of sites with bleeding on probing, and absence of functional dentition (

Background: Presence of cardiovascular disease (CVD) risk factors (RFs) should prompt patients and their providers to work aggressively towards controlling those that are modifiable. The extent to which a greater CVD RF burden is related to CVD RF control in a contemporary and diverse Hispanic/Latino population is not well-understood. Methods: Using multicenter community-based data from the Hispanic Community Health Study/Study of Latinos, we assessed the self-reported prevalence of hypertension, hypercholesterolemia, diabetes, and prevalent CVD (ischemic heart disease or stroke). We used contemporaneous guidelines to define RF control. Multivariable logistic regression for complex survey sampling was used to examine whether having more CVD RFs was associated with CVD RF control (adjusting for age, sex, Hispanic background group, education, and health insurance). Results: Our sample included 8521 participants with at least one CVD RF or prevalent CVD. The mean age in HCHS/SOL target population was 49 (SE 0.3) years and 56% were women. Frequency of one, two, or three self-reported CVD RFs was 57%, 26%, 8%, respectively, and overall 9% of participants had prevalent CVD. After adjusting for sociodemographic factors, compared to those reporting one CVD RF, individuals with three CVD RFs were the least likely to have blood pressure, cholesterol, and glucose optimally controlled (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.40–0.80). However, those with prevalent CVD were more likely to have all three risk factors controlled, (OR: 1.43; 95% CI: 1.01–2.01). Conclusion: Hispanic/Latino adults with three major CVD RFs represent a group with poor overall CVD RF control. Secondary CVD prevention fares better. The potential contributors to inadequate CVD RF control in this highly vulnerable group warrants further investigation.

Abstract Background Physical activity is a modifiable healthy behavior that has been shown to positively influence health-related quality of life. However, research examining the link between physical activity and health-related quality of life among Hispanic/Latino adults is limited and inconsistent. The purpose of this study is to assess whether accelerometer-measured moderate-vigorous physical activity (MVPA) is associated with self-reported (a) mental health-related quality of life, and (b) physical health-related quality of life among diverse Hispanic/Latino adults in the US. Methods Cross-sectional data from 12,379 adults ages 18–74 years in 2008–2011, who participated in HCHS/SOL and had complete data were analyzed using complex survey design methods. Accelerometer data were categorized into no MVPA, low, moderate, and high MVPA. Health-related quality of life was assessed with the Short-Form 12 and we used the mental and physical component subscales where higher scores indicate better health-related quality of life. Multivariate linear regression models were used to derive adjusted means with 95% confidence intervals and linear trends. Results We observed no significant linear trend between accelerometer-measured MVPA and mental health-related quality of life (ptrend = 0.73). There was a significant positive association between MVPA and physical health-related quality of life (ptrend

Estimated glomerular filtration rate (eGFR) is a measure of kidney function used to define chronic kidney disease. Here, Morris et al. perform trans-ethnic genome-wide meta-analyses for eGFR in 312,468 individuals and identify novel loci and downstream putative causal genes.

Abstract Background Many epidemiological studies test trends when investigating the association between a risk factor and a disease outcome. Continuous exposures are commonly discretized when the outcome is nonlinearly related to exposure as well as to facilitate interpretation and reduce measurement error. Guidance is needed regarding statistically valid trend tests for epidemiological data of this nature. Methods The association between a discretized variable and a disease is modeled through logistic regression or survival analysis. Linear regression is then conducted by regressing the odds ratio or relative risk on the midpoint of the exposure interval. The trend test is based on the slope of the regression line. In order to investigate the performance of this approach, we conducted simulation studies, considering ten different approaches for the linear regression based on the inclusion or exclusion of an intercept in the model and the form of the weights. The proposed methods are applied to the National Health and Nutrition Examination Survey (NHANES) 2007–2008 for illustration. Results The simulation studies show that eight of these methods are valid, and the relative efficiency depends on the underlying relationship between the covariate and the outcome. Conclusions The significance of the study is its potential to help practitioners select an appropriate method to test for trend in their future studies that utilize ordinal covariates.

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.

Background: Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants. Methods: We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity. Findings: When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10−11; METTL8, rs116951054, MAF 0.09%, P = 4.5 × 10−9; and MATK, rs539182790, MAF 0.05%, P = 3.4 × 10−9). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P = 1.2 × 10−9, nearest gene GATM, and rs71147340, MAF=0.34, P = 3.3 × 10−9, CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants. Interpretation: This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.

Background Among US Hispanics/Latinos, the largest ethnic minority population in the United States, hypertension incidence has not been thoroughly reported. The goal of this study was to describe the incidence of hypertension among US Hispanic/Latino men and women of diverse Hispanic/Latino background. Methods and Results We studied 6171 participants of the Hispanic Community Health Study/Study of Latinos, a diverse group of self‐identified Hispanics/Latinos from 4 US urban communities, aged 18 to 74 years, and free from hypertension in 2008 to 2011 and re‐examined in 2014 to 2017. Hypertension was defined as self‐reported use of anti‐hypertension medication, or measured systolic blood pressure ≥130 mm Hg, or diastolic blood pressure ≥80 mm Hg. Results were weighted given the complex survey design to reflect the target population. Among men, the 6‐year age‐adjusted probability of developing hypertension was 21.7% (95% CI, 19.5–24.1) and differed by Hispanic/Latino background. Specifically, the probability was significantly higher among men of Cuban (27.1%; 95% CI, 20.2–35.2) and Dominican (28.1%; 95% CI, 19.5–38.8) backgrounds compared with Mexican Americans (17.6%; 95% CI: 14.5–21.2). Among women, the 6‐year age‐adjusted probability of developing hypertension was 19.7% (95% CI, 18.1–21.5) and also differed by Hispanic/Latino background. Specifically, the probability was significantly higher among women of Cuban (22.6%; 95% CI, 18.3–27.5), Dominican (23.3%; 95% CI, 18.0–29.5), and Puerto Rican (28.2%; 95% CI, 22.7–34.4) backgrounds compared with Mexican Americans (16.0%; 95% CI, 13.9–18.4). Conclusions Hypertension incidence varies by Hispanic/Latino background, with highest incidence among those of Caribbean background.

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) < 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11-34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count 86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8x10-15] in African populations, rs11549407 with lower HGB [p = 1.5x10-12] and HCT [p = 8.8x10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations.

Hispanics/Latinos are burdened by chronic kidney disease (CKD). The role of acculturation in this population has not been explored. We studied the association of acculturation with CKD and cardiovascular risk factor control. We performed cross-sectional analyses of 13,164 U.S. Hispanics/Latinos enrolled in the HCHS/SOL Study between 2008 and 2011. Acculturation was measured using the language and ethnic social relations subscales of the Short Acculturation Scale for Hispanics, and proxies of acculturation (language preference, place of birth and duration of residence in U.S.). CKD was defined as estimated glomerular filtration rate (eGFR)

Allostatic load (AL), an index of biological “wear and tear” on the body from cumulative exposure to stress, has been little studied in US Hispanics/Latinos. We investigated AL accumulation patterns by age, sex, and nativity in the Hispanic Community Health Study/Study of Latinos. We studied 15,830 Hispanic/Latinos of Mexican, Cuban, Dominican, Puerto Rican, Central and South American descent aged 18–74 years, 77% of whom were foreign-born. Consistent with the conceptualization of AL, we developed an index based upon 16 physiological markers that spanned the cardiometabolic, parasympathetic, and inflammatory systems. We computed mean adjusted AL scores using log-linear models across age-groups (18–44, 45–54, 55–74 years), by sex and nativity status. Among foreign-born individuals, differences in AL by duration of residence in the US (

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.

Background. Individuals with “metabolically healthy obesity” (MHO) phenotype (i.e., obesity and absence of cardiometabolic abnormalities: favorable levels of blood pressure, lipids, and glucose) experience lower risk of cardiovascular disease compared with those with “metabolically at-risk obesity” (MAO) phenotype (i.e., obesity with concurrent cardiometabolic abnormalities). Among Hispanic/Latino women and men with obesity, limited data exist on the correlates of and body composition measures associated with obesity phenotypes. Methods. Data from the Hispanic Community Health Study/Study of Latinos (2008–2011) were used to estimate the age-adjusted distribution of obesity phenotypes among 5,426 women and men (aged 20–74 years) with obesity (BMI ≥ 30 kg/m2) and to compare characteristics between individuals with MHO and MAO phenotypes. Weighted Poisson regression models were used to examine cross-sectional associations between 1-standard deviation (SD) increase in body composition measures (i.e., body fat percentage, waist circumference, and body lean mass) and MHO phenotype prevalence. Results. The age-adjusted proportion of the MHO phenotype was low (i.e., 12.5% in women and 6.5% in men). In bivariate analyses, women and men with the MHO phenotype were more likely to be younger, have higher education and acculturation levels, report lower lifetime cigarette use, and have fasting insulin and waist circumference levels than MAO. Adjusting for sociodemographic and lifestyle factors, among women, each 1-SD increase in body fat percentage, waist circumference, and lean body mass was, respectively, associated with a 21%, 33%, and 31% lower prevalence of the MHO phenotype. Among men, each 1-SD increase in waist circumference and lean body mass was, respectively, associated with a 20% and 15% lower prevalence of the MHO phenotype. Conclusions. We demonstrated that higher waist circumference and higher lean body mass were independently associated with a lower proportion of the MHO phenotype in Hispanic/Latino women and men. Findings support the need for weight reduction interventions to manage cardiometabolic health among Hispanics/Latinos.

[This corrects the article DOI: 10.1371/journal.pgen.1006728.].

OBJECTIVES:Religion plays an important role in the lives of people in the United States. We examined the prevalence of religiosity among Hispanic/Latinos in four regions of the United States and looked at its correlation to depression and anxiety symptoms. DESIGN:The population-based Hispanic Community Health Study/ Study of Latinos enrolled a cohort of Hispanic/Latino adults (N = 16,415) ages 18-74 in four US cities from June 2008 to June 2011. Participants with complete data on religiosity (i.e., religious affiliation, frequency of attending religious activities and importance of religion), depression (assessed with the CESD-10), and trait anxiety (assessed with the STAI-10) were included in the present study. Distribution of religiosity is described by sociodemographic characteristics. Associations between religiosity with depression and anxiety were examined with logistic regression models controlling for sex, age group, education, Hispanic/Latino background, clinical center, and nativity. RESULTS:The majority of the population (89.5%) reported having a religious affiliation. Weekly attendance at religious activities was reported by 41.6% of participants, while 20.6% did not attend any religious activities. Religion was very important to 63.9% and not at all important to 6.7% of the population. The CES-D scores and trait anxiety scores were not significantly related in the overall group to frequency of attending religious activity or perceived importance of religion. However, in age-stratified analyses, among older individuals (65+ years old) reporting "never" participating in religious activities compared to more than once per week was associated with an 80% higher likelihood of having high depressive symptomatology. Similarly, in the older age group, no religious affiliation or reporting that religion is "not at all important" was associated with greater anxiety symptomatology. CONCLUSION:Religiosity varied by Hispanic/Latino background. Lack of religiosity was associated with elevated depressive or anxiety symptomology in older adults but not in young or middle-aged adults.

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

Although recent studies show an improved survival of children with sickle cell disease in the US and Europe, for adult patients mortality remains high. This study was conducted to evaluate the factors associated with mortality in adult patients following the approval of hydroxyurea. We first evaluated the association between selected variables and mortality at an academic center (University of North Carolina). Data sources were then searched for publications from 1998 to June 2016, with meta-analysis of eligible studies conducted in North America and Europe to evaluate the associations of selected variables with mortality in adult patients. Nine studies, combined with the UNC cohort (total n=3257 patients) met the eligibility criteria. Mortality was significantly associated with age (per 10-year increase in age) [7 studies, 2306 participants; hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.10–1.50], tricuspid regurgitant jet velocity 2.5 m/s or more (5 studies, 1577 participants; HR: 3.03; 95%CI: 2.0–4.60), reticulocyte count (3 studies, 1050 participants; HR: 1.05; 95%CI: 1.01–1.10), log(N-terminal-pro-brain natriuretic peptide) (3 studies, 800 participants; HR: 1.68; 95%CI: 1.48–1.90), and fetal hemoglobin (7 studies, 2477 participants; HR: 0.97; 95%CI: 0.94–1.0). This study identifies variables associated with mortality in adult patients with sickle cell disease in the hydroxyurea era.