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Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p

We studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)-the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed their association with MCI in datasets of diverse race/ethnicities. We first performed a GWAS for the MCI-MRS and BAIBA, in Hispanic/Latino adults (n = 3890) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We identified ten independent genome-wide significant (p value

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.

Inequalities are everywhere, yet little is known about how children respond to people affected by inequalities. This article explores two responses--minimizing inequalities and favoring those who are advantaged by them. In Studies 1a (N = 37) and 1b (N = 38), 4- and 5-year-olds allocated a resource to a disadvantaged recipient, but judged advantaged recipients more positively. In Studies 2 (N = 38) and 3 (N = 74), a delay occurred between seeing the inequality and allocating resources, or stating a preference, during which time participants forgot who was initially more advantaged. Children then favored advantaged recipients on the preference and resource allocation measures, suggesting an implicit "affective tagging" mechanism drives the tendency to favor the advantaged. In contrast, reducing inequalities through resource allocation appears to require explicit reasoning.

A suprising pattern in the local maladaptation in the soft scale insect Saissetia Coffeae (Hemiptera: Coccidae) at the host species level is discussed. It is seen that the some aspects of the biology of S. coffeae may impair its ability to adapt to local selection pressures, however, scale insects are often locally adapted on fine spatial scales and therefore local maladaptation is very surprising.

The belief that personality is fixed (an entity theory of personality) can give rise to negative reactions to social adversities. Three studies showed that when social adversity is common-at the transition to high school-an entity theory can affect overall stress, health, and achievement. Study I showed that an entity theory of personality, measured during the 1St month of 9th grade, predicted more negative immediate reactions to social adversity and, at the end of the year, greater stress, poorer health, and lower grades in school. Studies 2 and 3, both experiments, tested a brief intervention that taught a malleable (incremental) theory of personality-the belief that people can change. The incremental theory group showed less negative reactions to an immediate experience of social adversity and, 8 months later, reported lower overall stress and physical illness. They also achieved better academic performance over the year. Discussion centers on the power of targeted psychological interventions to effect far-reaching and long-term change by shifting interpretations of recurring adversities during developmental transitions. [ABSTRACT FROM AUTHOR]

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup. We define a metric called "expected PRS" (ePRS), the expected value of a PRS based on one's global or local admixture patterns. We further define the "residual PRS" (rPRS), measuring the deviation of the PRS from the ePRS. Simulation studies confirm that it suffices to adjust for ePRS to obtain nearly unbiased estimates of the PRS-outcome association without further adjusting for PCs. Using the TOPMed dataset, the estimated effect size of the rPRS adjusting for the ePRS is similar to the estimated effect of the PRS adjusting for genetic PCs. Similarly, we applied the ePRS framework to six cardiovascular-related traits in the All of Us dataset, and the results are consistent with those from the TOPMed analysis. The ePRS framework can protect from population stratification in association analysis and provide an equitable strategy to quantify genetic risk across diverse populations., Competing Interests: Competing interests BP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. LMR and SSR are consultants to the TOPMed Administrative Coordinating Center (through Westat®).

Obstructive sleep apnea (OSA) is a multifactorial sleep disorder characterized by a strong genetic basis. Excessive daytime sleepiness (EDS) is a symptom that is reported by a subset of OSA patients, persisting even after treatment with continuous positive airway pressure (CPAP). It is recognized as a clinical subtype underlying OSA carrying alarming heightened cardiovascular risk. Thus, conceptualizing EDS as an exposure variable, we sought to investigate EDS's influence on genetic variation linked to apnea-hypopnea index (AHI), a diagnostic measure of OSA severity. This study serves as the first large-scale genome-wide gene x environment interaction analysis for AHI, investigating the interplay between its genetic markers and EDS across and within specific sex. Our work pools together whole genome sequencing data from seven cohorts, enabling a diverse dataset (four population backgrounds) of over 11,500 samples. Among the total 16 discovered genetic targets with interaction evidence with EDS, eight are previously unreported for OSA, including CCDC3 , MARCHF1 , and MED31 identified in all sexes; TMEM26 , CPSF4L , and PI4K2B identified in males; and RAP1GAP and YY1 identified in females. We discuss connections to insulin resistance, thiamine deficiency, and resveratrol use that may be worthy of therapeutic consideration for excessively sleepy OSA patients., Competing Interests: Competing Interests: LMR is a consultant for the TOPMed Administrative Coordinating Center (through Westat).

Background: Coronary heart disease (CHD) is a leading cause of death for Hispanic/Latino populations in the United States. We evaluated polygenic risk scores (PRS) with incident myocardial infarction (MI) in a Hispanic/Latino study sample., Methods: We leveraged data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) to assess four CHD-PRS from the PGS catalog, derived using multiple methods (LDpred, AnnoPred, stacked clumping and thresholding, and LDPred2). We evaluated associations between each standardized PRS and time to adjudicated incident MI, adjusted for age, sex, first 5 principal components, and weighted for survey design. Concordance statistics (c-index) compared predictive accuracy of each PRS with, and in addition to, traditional risk factors (TRF) for CHD (obesity, hypercholesterolemia, hypertension, diabetes, and smoking). Analyses were stratified by self-reported Caribbean- (Puerto Rican, Dominican or Cuban) and Mainland-(those of Mexican, Central American, or South American) heritage subgroups., Results: After 11 years follow-up, for 9055 participants (mean age (SD) 47.6(13.1), 62.2% female), the incidence of MI was 1.0% (n = 95). Each PRS was more strongly associated with MI among Mainland participants. LDPred2 + TRF performed best among the Mainland subgroup; HR=2.69, 95% CI [1.71, 4.20], c-index = 0.897, 95% CI [0.848, 0.946]; a modest increase over TRF alone, c-index = 0.880, 95% CI [0.827, 0.933]. AnnoPred + TRF performed best among the Caribbean sample; c-index = 0.721, 95% CI [0.647, 0.795]; however, was not significantly associated with rate of MI (HR=1.14, 95% CI [0.82, 1.60])., Conclusion: PRS performance for CHD is lacking for Hispanics/Latinos of Caribbean origin who have substantial proportions of African genetic ancestry, risking increased health disparities. AnnoPred, using functional annotations, outperformed other PRS in the Caribbean subgroup, suggesting a potential strategy for PRS construction in diverse populations. These results underscore the need to optimize cumulative genetic risk prediction of CHD in diverse Hispanic/Latino populations.

Objective: We sought to evaluate whether obstructive sleep apnea (OSA), and other sleep disorders, increase genetic risk of developing diabetes mellitus (DM)., Research Design and Methods: Using GWAS summary statistics from the DIAGRAM consortium and Million Veteran Program, we developed multi-ancestry Type 2 Diabetes (T2D) polygenic risk scores (T2D-PRSs) useful in admixed Hispanic/Latino individuals. We estimated the association of the T2D-PRS with cross-sectional and incident DM in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We conducted a mediation analysis with T2D-PRSs as an exposure, incident DM as an outcome, and OSA as a mediator. Additionally, we performed Mendelian randomization (MR) analysis to assess the causal relationship between T2D and OSA., Results: Of 12,342 HCHS/SOL participants, at baseline, 48.4% were normoglycemic, 36.6% were hyperglycemic, and 15% had diabetes, and 50.9% identified as female. Mean age was 41.5, and mean BMI was 29.4. T2D-PRSs was strongly associated with baseline DM and with incident DM. At baseline, a 1 SD increase in the primary T2D-PRS had DM adjusted odds ratio (OR) = 2.67, 95% CI [2.40; 2.97] and a higher incident DM rate (incident rate ratio (IRR) = 2.02, 95% CI [1.75; 2.33]). In a stratified analysis based on OSA severity categories the associations were stronger in individuals with mild OSA compared to those with moderate to severe OSA. Mediation analysis suggested that OSA mediates the T2D-PRS association with DM. In two-sample MR analysis, T2D-PRS had a causal effect on OSA, OR = 1.03, 95% CI [1.01; 1.05], and OSA had a causal effect on T2D, with OR = 2.34, 95% CI [1.59; 3.44]., Conclusions: OSA likely mediates genetic effects on T2D., Competing Interests: Competing interests Dr. Redline discloses consulting relationships with Eli Lilly Inc. Additionally, Dr. Redline serves as an unpaid member of the Apnimed Scientific Advisory Board, as an unpaid board member for the Alliance for Sleep Apnoea Partners and for the National Sleep Foundation.

Introduction: DNA methylation (DNAm) predictors of high sensitivity C-reactive protein (CRP) offer a stable and accurate means of assessing chronic inflammation, bypassing the CRP protein fluctuations secondary to acute illness. Poor sleep health is associated with elevated inflammation (including elevated blood CRP levels) which may explain associations of sleep insufficiency with metabolic, cardiovascular and neurological diseases. Our study aims to characterize the relationships among sleep health phenotypes and CRP markers -blood, genetic, and epigenetic indicators-within the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)., Methods: In HCHS/SOL, methylation risk scores (MRS)-CRP and polygenetic risk score (PRS)-CRP were constructed separately as weighted sums of methylation beta values or allele counts, respectively, for each individual. Sleep health phenotypes were measured using self-reported questionnaires and objective measurements. Survey-weighted linear regression established the association between the multiple sleep phenotypes (obstructive sleep apnea (OSA), sleep duration, insomnia and excessive sleepiness symptom), cognitive assessments, diabetes and hypertension with CRP markers while adjusting for age, sex, BMI, study center, and the first five principal components of genetic ancestry in HCHS/SOL., Results: We included 2221 HCHS/SOL participants (age range 37-76 yrs, 65.7% female) in the analysis. Both the MRS-CRP (95% confidence interval (CI): 0.32-0.42, p = 3.3 × 10 -38 ) and the PRS-CRP (95% CI: 0.15-0.25, p = 1 × 10 -14 ) were associated with blood CRP level. Moreover, MRS-CRP was associated with sleep health phenotypes (OSA, long sleep duration) and related conditions (diabetes and hypertension), while PRS-CRP markers were not associated with these traits. Circulating CRP level was associated with sleep duration and diabetes. Associations between OSA traits and metabolic comorbidities weakened after adjusting for MRS-CRP, most strongly for diabetes, and least for hypertension., Conclusions: MRS-CRP is a promising estimate for systemic and chronic inflammation as reflected by circulating CRP levels, which either mediates or serves as a common cause of the association between sleep phenotypes and related comorbidities, especially in the presence of diabetes.

Sleep is essential to maintaining health and wellbeing of individuals, influencing a variety of outcomes from mental health to cardiometabolic disease. This study aims to assess the relationships between various sleep phenotypes and blood metabolites. Utilizing data from the Hispanic Community Health Study/Study of Latinos, we performed association analyses between 40 sleep phenotypes, grouped in several domains (i.e., sleep disordered breathing (SDB), sleep duration, timing, insomnia symptoms, and heart rate during sleep), and 768 metabolites measured via untargeted metabolomics profiling. Network analysis was employed to visualize and interpret the associations between sleep phenotypes and metabolites. The patterns of statistically significant associations between sleep phenotypes and metabolites differed by superpathways, and highlighted subpathways of interest for future studies. For example, some xenobiotic metabolites were associated with sleep duration and heart rate phenotypes (e.g. 1H-indole-7-acetic acid, 4-allylphenol sulfate), while ketone bodies and fatty acid metabolism metabolites were associated with sleep timing measures (e.g. 3-hydroxybutyrate (BHBA), 3-hydroxyhexanoylcarnitine (1)). Heart rate phenotypes had the overall largest number of detected metabolite associations. Many of these associations were shared with both SDB and with sleep timing phenotypes, while SDB phenotypes shared relatively few metabolite associations with sleep duration measures. A number of metabolites were associated with multiple sleep phenotypes, from a few domains. The amino acids vanillylmandelate (VMA) and 1-carboxyethylisoleucine were associated with the greatest number of sleep phenotypes, from all domains other than insomnia. This atlas of sleep-metabolite associations will facilitate hypothesis generation and further study of the metabolic underpinnings of sleep health., Competing Interests: Declaration of interests Dr. Redline discloses consulting relationships with Eli Lilly Inc. Additionally, Dr. Redline serves as an unpaid member of the Apnimed Scientific Advisory Board, as an unpaid board member for the Alliance for Sleep Apnoea Partners, and has received loaned equipment for a multi-site study: oxygen concentrators from Philips Respironics and polysomnography equipment from Nox Medical.

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, and together may provide a more complete picture of sleep health, while also illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p<8.3e-9), along with 341 previously reported loci (p<5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h 2 =0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections to behavioral, psychological, and cardiometabolic traits.