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Introduction Excessive daytime sleepiness is associated with multiple sleep, cardiometabolic, and neuropsychiatric disorders. Previous genome-wide association studies (GWAS) of daytime sleepiness using a single question in European population revealed associations for multiple genes in central nervous pathways. However, findings are still limited and may not be generalizable to other populations. In this study, we performed the first whole-genome sequence (WGS) analyses for Epworth Sleepiness Scale (ESS) in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. Methods This study includes 15,201 individuals of diverse race and ethnic backgrounds from seven cohorts in the TOPMed. We performed GWAS of single common variants (MAF>0.01) and gene-based burden tests of low-frequency and rare functional variants (loss of function and missense; MAF< 0.05). We adjusted for age, sex, body mass index (BMI), study, race/ethnicity, and genetic relatedness using linear mixed effects models implemented in the GENESIS R package. Results This sample included 43.8% males with a mean age of 54.9 years and BMI 29.6kg/m2, of whom 21.3% were classified with excessive daytime sleepiness (ESS>=10). In single variant test, we identified one novel genomic locus at rs60249969 (on CELF2) significantly associated with ESS (p-value=3.91x10-8). Suggestive significant associations were observed at 5 novel loci that overlapped with PDE7A/DNAJC5B, AHI1/PDE7B, KCNH7, F5, and FBXL17 (p< 1x10-7). In gene-based burden test, we did not identify any gene significantly associated with the ESS after correcting for multiple comparisons (p< 2x10-6). Suggestive significant evidence was observed at OR1A2 (consisting of 41 missense variants; p-value=1.65x10-5), an olfactory receptor gene differentially expressed in choroid plexus in the brain implicated in neurodegenerative diseases. Conclusion In our investigation of common and rare variant associations with excessive daytime sleepiness as assessed by the ESS, we identified one significant and several suggestive novel loci that mapped to genes highly expressed in brain tissues, which may have implications on sleep wake control system. Our next step will include replication analyses using independent imputed samples. Support (if any) R01HL153814 (to H.W.), NHLBI R35HL135818 (to S.R.).

Simvastatin is used along with a proper diet to help lower bad cholesterol and fats and raise good cholesterol in the blood. It belongs to a group of drugs known as statins. It works by reducing the amount of cholesterol made by the liver. Lowering bad cholesterol and triglycerides and raising good cholesterol decreases the risk of heart disease and helps prevent strokes and heart attacks. There are various analytical methods for estimation of the drug. This paper list outs the various analytical methods for the drug.

Introduction Recent genome-wide association studies (GWAS) of individual sleep traits have identified hundreds of genetic loci, often implicating genes and biological pathways that are shared across sleep phenotypes. Modeling multiple dimensions of sleep may allow identification of common underlying genetic mechanisms and complement analyses of individual traits. Moreover, construction of novel sleep health scores, accounting for correlations between traits, has the potential to enhance specificity and power for genetic analyses. Methods We performed GWAS of composite sleep scores derived from five sleep questions characterizing 413,904 individuals of European ancestry from the UK Biobank. We constructed an additive sleep score (SS-add) as a sum of up to five favorable self-reported sleep behaviors (sleep duration of 7-8 hours, early chronotype, few insomnia symptoms, no snoring, and no excessive daytime sleepiness) as well as five principal component scores (SS-PC1 – SS-PC5) using the underlying sleep traits. SNP-level association studies of the sleep scores were complemented with multiple follow-up analyses, including investigation of pathway, tissue, and cell-type enrichments, as well as comprehensive genetic correlation (381 representative phenotypes) and bi-directional Mendelian randomization (MR) analyses (40 selected phenotypes). Results Sleep scores SS-PC1 (interpretable as longer duration sleep without insomnia symptoms) and SS-PC2 (healthy sleep without snoring or sleepiness) showed higher heritability (respectively 11.7% and 9.3%) compared with their primary underlying traits. SS-PC3 (loading strongly on chronotype) showed highest overall heritability (15.3%). Accounting for the six GWAS, we identified 28 significant novel loci (p< 8.3e-9), 31 additional novel loci (p< 5e-8), and 341 loci previously reported (p< 5e-8) by GWAS of individual sleep traits. Associated loci mapped to genes enriched in expression in brain tissues, and in metabolic and neuronal pathways. Numerous neurological, cardiometabolic and other traits were genetically correlated with sleep health (104 with|rho_g|>0.3, p< 2e-5). MR associations (p< 2e-4) pointed to causes (BMI [SS-PC2/PC4], smoking [SS-add/PC1], lower socio-economic status [SS-add/PC5]) and consequences (coronary heart disease [SS-add/PC1], pain [SS-PC1/5]) of poor sleep. Conclusion Composite sleep health scores revealed novel genetic mechanisms of related sleep behaviors, helped clarify relationships with neurological and cardiometabolic traits, and deserve further investigation. Support (if any) R01HL153814 (to H.W.), NHLBI R35HL135818 (to S.R.), 1R01HL146751 (to R.S.), UKB Application 6818.

This article explores how a single-sex school for boys of color intentionally and unintentionally (re)defines masculinity through rules and rituals. The school’s mission posits that boys become men through developing three skills: selfregulation, self-awareness, and self-reflection. Drawing from qualitative research data, I examine how disciplinary practices prioritize boys’ ability to control their bodies and image, or “self-regulate.” When boys fail to self-regulate, they enter the punitive system. School staff describe self-regulation as integral to out-of-school success, but these practices may inadvertently reproduce negative labeling and control of black bodies. This article argues for school cultural practices that affirm, rather than deny, the benefits of boyhood.