Untargeted Metabolome Atlas for Sleep Phenotypes in the Hispanic Community Health Study/Study of Latinos.

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.

Genome-wide association analysis of composite sleep health scores in 413,904 individuals.

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-h2=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.

Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment.

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 <5 × 10-8) variants associated with MCI-MRS or BAIBA. Variants associated with the MCI-MRS are located in the Alanine-Glyoxylate Aminotransferase 2 (AGXT2 gene), which is known to be associated with BAIBA metabolism. Variants associated with BAIBA are located in the AGXT2 gene and in the SLC6A13 gene. Next, we tested the variants' association with MCI in independent datasets of n = 3178 HCHS/SOL older individuals, n = 3775 European Americans, and n = 1032 African Americans from the Atherosclerosis Risk In Communities (ARIC) study. Variants were considered associated with MCI if their p value <0.05 in the meta-analysis of the three datasets and their direction of association was consistent with expectation. Rs16899972 and rs37369 from the AGXT2 region were associated with MCI. Mediation analysis supported the mediation effect of BAIBA between the two genetic variants and MCI (p value = 0.004 for causal mediated effect). In summary, genetic variants in the AGXT2 region are associated with MCI in Hispanic/Latino, African, and European American populations in the USA, and their effect is likely mediated by changes in BAIBA levels.

Interaction analysis of ancestry-enriched variants with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging.

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.

Genetic determinants of cardiometabolic and pulmonary phenotypes and obstructive sleep apnoea in HCHS/SOL.

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<0.05), and of OSA. We studied the association of the PRSs of the correlated phenotypes with both REI and OSA (REI≥5), and the association of OSA PRS with the correlated phenotypes. Causal relationships were tested using Mendelian Randomization (MR) analysis. FINDINGS: The dataset included 11,155 participants, 31.03% with OSA. 22 phenotypes were genetically correlated with REI. 10 PRSs covering obesity and fat distribution (BMI, WHR, WHRadjBMI), blood pressure (DBP, PP, MAP), glycaemic control (fasting insulin, HbA1c, HOMA-B) and insomnia were associated with REI and/or OSA. OSA PRS was associated with BMI, WHR, DBP and glycaemic traits (fasting insulin, HbA1c, HOMA-B and HOMA-IR). MR analysis identified robust causal effects of BMI and WHR on OSA, and probable causal effects of DBP, PP, and HbA1c on OSA/REI. INTERPRETATION: There are shared genetic underpinnings of anthropometric, blood pressure, and glycaemic phenotypes with OSA, with evidence for causal relationships between some phenotypes. FUNDING: Described in Acknowledgments.

When Societal Norms and Social Identity Collide: the Race Talk Dilemma for Racial Minority Children.

Racial minorities face a unique "race talk" dilemma in contemporary American society: their racial background is often integral to their identity and how others perceive them, yet talk of race is taboo. This dilemma highlights the conflict between two fundamental social processes: social identity development and social norm adherence. To examine how, and with what costs, this dilemma is resolved, 9-12-year-old Latino, Asian, Black, and White children (n=108) completed a photo identification task in which acknowledging racial difference is beneficial to performance. Results indicate minority children are just as likely to avoid race as White children, and such avoidance exacted a cost to performance and nonverbal comfort. Results suggest that teachers are particularly important social referents for instilling norms regarding race. Norms that equate colorblindness with socially appropriate behavior appear more broadly influential than previously thought, stifling talk of race even among those for whom it may be most meaningful.

Minding and mending the gap: Social psychological interventions to reduce educational disparities.

BACKGROUND: Achievement gaps continue to garner a great deal of attention both in academic and in popular circles. Many students continue to struggle despite broad educational reforms aimed at narrowing these gaps in learning and performance. AIMS: In this article, we review a number of social psychological interventions that show promise in reducing gaps in achievement, not by addressing structural barriers to achievement, but by helping students cope with threats to their identity that impair intellectual functioning and motivation. For example, interventions involving meditation, role models, emotional reappraisal, growth mindsets, imagining possible selves, self-affirmations, belongingness and cooperative learning have been shown to ameliorate threats to identity and raise achievement. We describe and evaluate these social psychological interventions. ARGUMENTS: Many achievement gaps involve a psychological predicament: a threat to one's social identity or to one's sense of belonging. Students' implicit theories - how they mind the gap - can act as barriers to their success. By helping students cope with these threats, these theory-based interventions represent a genuine advance in the way schools may reduce gaps in achievement. CONCLUSION: These interventions show how students' educational success depends partly on fluid aspects of context - how tasks are framed, who else is in the room, or what they believe about intelligence. Because of this fluidity, these interventions may not work in all settings. Achievement gaps are ultimately caused by a variety of factors, both objective and subjective that produce inequality. The research reviewed here suggests that even without changes in objective barriers to success, brief psychological interventions can narrow what many see as intractable gaps in academic achievement.

Boring but important: a self-transcendent purpose for learning fosters academic self-regulation.

Many important learning tasks feel uninteresting and tedious to learners. This research proposed that promoting a prosocial, self-transcendent purpose could improve academic self-regulation on such tasks. This proposal was supported in 4 studies with over 2,000 adolescents and young adults. Study 1 documented a correlation between a self-transcendent purpose for learning and self-reported trait measures of academic self-regulation. Those with more of a purpose for learning also persisted longer on a boring task rather than giving in to a tempting alternative and, many months later, were less likely to drop out of college. Study 2 addressed causality. It showed that a brief, one-time psychological intervention promoting a self-transcendent purpose for learning could improve high school science and math grade point average (GPA) over several months. Studies 3 and 4 were short-term experiments that explored possible mechanisms. They showed that the self-transcendent purpose manipulation could increase deeper learning behavior on tedious test review materials (Study 3), and sustain self-regulation over the course of an increasingly boring task (Study 4). More self-oriented motives for learning--such as the desire to have an interesting or enjoyable career--did not, on their own, consistently produce these benefits (Studies 1 and 4).

The far-reaching effects of believing people can change: implicit theories of personality shape stress, health, and achievement during adolescence.

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 1 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.

Preschoolers reduce inequality while favoring individuals with more.

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 (N = 38) and (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.

Migration load and the coexistence of ecologically similar sexuals and asexuals.

The frozen niche variation hypothesis suggests that sexuals can coexist with closely related, ecologically similar asexuals because sexuals and narrowly adapted asexual clones use different resources. However, because a collection of clones can potentially dominate the entire resource axis, such coexistence is not stable. We show that if the sexual population inhabits multiple selection regimes and asexuals are intrinsically slightly less fit than sexuals, migration load in the sexual population allows sexuals and asexuals to coexist stably at the regional level. By decreasing sexuals' fitness, migration load allows asexuals to invade the sexual population. However, as the sexuals' range contracts, migration load decreases, preventing asexuals from driving sexuals to extinction. This "buffering" effect of migration load is even more relevant in models that include more realistic conditions, such as demographic asymmetries or explicit spatial structure.

Local maladaptation in the soft scale insect Saissetia coffeae (Hemiptera: Coccidae).

Local adaptation has often been documented in herbivorous insects. The potential for local maladaptation in phytophagous insects, however, has not been widely considered. I performed a two-generation reciprocal cross-transplant experiment with the generalist soft scale insect Saissetia coffeae (Hemiptera: Coccidae) on two common species of host plants in rain forest habitat in Costa Rica. In this system, S. coffeae showed significant local maladaptation at the level of the host species. Lineages originally collected from Witheringia enjoyed a strong advantage over those collected from Lomariopsis when both sets of lineages were placed on Lomariopsis; however, when both sets of lineages were raised on Witheringia, their fitnesses were statistically indistinguishable. While some aspects of the biology of S. coffeae may impair its ability to adapt to local selection pressures, scale insects are often locally adapted on fine spatial scales, and local maladaptation is therefore especially surprising. Other documented cases of local maladaptation in parasites appear to be due to evolution on the part of the host. The possibility that hosts or natural enemies may place local genotypes at a disadvantage, producing a pattern of local maladaptation, is one that deserves more consideration in the context of plant-insect interactions.

Maternal effects in the soft scale insect Saissetia coffeae (Hemiptera: Coccidae).

Effects of maternal environment on offspring performance have been documented frequently in herbivorous insects. Despite this, very few cases exist in which exposure of parent insects to a resource causes the phenotype of their offspring to be adjusted in a manner that is adaptive for that resource, a phenomenon called adaptive transgenerational phenotypic plasticity. I performed a two-generation reciprocal cross-transplant experiment in the field with the soft scale insect Saissetia coffeae (Hemiptera: Coccidae) on two disparate host plant species in order to separate genetic effects from possible transgenerational plasticity. Despite striking differences in quality between host species, maternal host had no effect on overall offspring performance, and I detected no "acclimatization" to the maternal host species. However, there was a significant negative association between maternal and offspring development times, with potentially adaptive implications. Furthermore, offspring of mothers reared in an environment where scale densities were higher and scales were more frequently killed by fungi were significantly less likely to suffer from fungal attack than were offspring of mothers reared in an environment where densities were low and fungal attack was rare. Although S. coffeae does not appear to alter offspring phenotype to increase offspring fitness on these two distinct plant species, it does appear that offspring phenotype may be responding to some subtler aspects of maternal environment. In particular, the possibility of induced transgenerational prophylaxis in S. coffeae deserves further investigation.