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1.
Kidney Int ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774559

RESUMO

Circulating metabolites are by-products of endogenous metabolism or exogenous sources and may inform disease states. Our study aimed to identify the source of variability in the association of metabolites with estimated glomerular filtration rate (eGFR) in Hispanics/Latinos with low chronic kidney disease prevalence and tested the association of 640 metabolites in 3,906 participants of the Hispanic Community Health Study/Study of Latinos. Metabolites were quantified in fasting serum through non-targeted mass spectrometry analysis. eGFR was regressed on inverse normally transformed metabolites in models accounting for study design and covariates. To identify the source of variation on eGFR associations, we tested the interaction of metabolites with lifestyle and clinical risk factors with results integrated with genotypes to identify metabolite genetic regulation. The mean age was 46 years, 43% were men, 22% were current smokers, 47% had a Caribbean Hispanic background, 19% had diabetes and the mean cohort eGFR was 96.4 ml/min/1.73 m2. We identified 404 eGFR-metabolite associations (False Discovery Rate under 0.05). Of these, 69 were previously reported, and 79 were novel associations with eGFR replicated in one or more published studies. There were significant interactions with lifestyle and clinical risk factors, with larger differences in eGFR-metabolite associations within strata of age, urine albumin to creatinine ratio, diabetes and Hispanic/Latino background. Several newly identified metabolites were genetically regulated, and variants were located at genomic regions previously associated with eGFR. Thus, our results suggest complex mechanisms contribute to the association of eGFR with metabolites and provide new insights into these associations.

2.
Ethn Dis ; 31(4): 547-558, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720558

RESUMO

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

3.
HGG Adv ; 2(3)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34337551

RESUMO

Whole-genome sequencing (WGS) and whole-exome sequencing studies have become increasingly available and are being used to identify rare genetic variants associated with health and disease outcomes. Investigators routinely use mixed models to account for genetic relatedness or other clustering variables (e.g., family or household) when testing genetic associations. However, no existing tests of the association of a rare variant with a binary outcome in the presence of correlated data control the type 1 error where there are (1) few individuals harboring the rare allele, (2) a small proportion of cases relative to controls, and (3) covariates to adjust for. Here, we address all three issues in developing a framework for testing rare variant association with a binary trait in individuals harboring at least one risk allele. In this framework, we estimate outcome probabilities under the null hypothesis and then use them, within the individuals with at least one risk allele, to test variant associations. We extend the BinomiRare test, which was previously proposed for independent observations, and develop the Conway-Maxwell-Poisson (CMP) test and study their properties in simulations. We show that the BinomiRare test always controls the type 1 error, while the CMP test sometimes does not. We then use the BinomiRare test to test the association of rare genetic variants in target genes with small-vessel disease (SVD) stroke, short sleep, and venous thromboembolism (VTE), in whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program.

4.
Genome Med ; 13(1): 136, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446064

RESUMO

BACKGROUND: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. METHODS: The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation < 90%. We adjusted for age, sex, BMI, study, and family structure using MMSKAT and EMMAX mixed linear model approaches. Additional bioinformatics analyses were performed with MetaXcan, GIGSEA, and ReMap. RESULTS: We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10-8) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways. CONCLUSIONS: We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response.

5.
Sleep ; 44(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34283244

RESUMO

STUDY OBJECTIVES: In an older African-American sample (n = 231) we tested associations of the household environment and in-bed behaviors with sleep duration, efficiency, and wakefulness after sleep onset (WASO). METHODS: Older adult participants completed a household-level sleep environment questionnaire, a sleep questionnaire, and underwent 7-day wrist actigraphy for objective measures of sleep. Perceived household environment (self-reported) was evaluated using questions regarding safety, physical comfort, temperature, noise, and light disturbances. In-bed behaviors included watching television, listening to radio/music, use of computer/tablet/phone, playing video games, reading books, and eating. To estimate the combined effect of the components in each domain (perceived household environment and in-bed behaviors), we calculated and standardized a weighted score per sleep outcome (e.g. duration, efficiency, WASO), with a higher score indicating worse conditions. The weights were derived from the coefficients of each component estimated from linear regression models predicting each sleep outcome while adjusting for covariates. RESULTS: A standard deviation increase in an adverse household environment score was associated with lower self-reported sleep duration (ß = -13.9 min, 95% confidence interval: -26.1, -1.7) and actigraphy-based sleep efficiency (ß = -0.7%, -1.4, 0.0). A standard deviation increase in the in-bed behaviors score was associated with lower actigraphy-based sleep duration (ß = -9.7 min, -18.0, -1.3), sleep efficiency (ß = -1.2%, -1.9, -0.6), and higher WASO (5.3 min, 2.1, 8.6). CONCLUSION: Intervening on the sleep environment, including healthy sleep practices, may improve sleep duration and continuity among African-Americans.

6.
Nat Commun ; 12(1): 3506, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108454

RESUMO

In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we term 'variance stratification'. Unaccounted for, variance stratification can lead to both decreased statistical power, and increased false positives rates, depending on how allele frequencies, sample sizes, and phenotypic variances vary across the studies that are pooled. We develop a procedure to compute variant-specific inflation factors, and show how it can be used for diagnosis of genetic association analyses on pooled individual level data from multiple studies. We describe a WGS-appropriate analysis approach, implemented in freely-available software, which allows study-specific variances and thereby improves performance in practice. We illustrate the variance stratification problem, its solutions, and the proposed diagnostic procedure, in simulations and in data from the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed), used in association tests for hemoglobin concentrations and BMI.


Assuntos
Variação Genética , Estudo de Associação Genômica Ampla/métodos , Algoritmos , Simulação por Computador , Frequência do Gene , Estudo de Associação Genômica Ampla/normas , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Fenótipo , Tamanho da Amostra
7.
EBioMedicine ; 68: 103433, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34144485

RESUMO

BACKGROUND: Multiple aspects of sleep and Sleep Disordered Breathing (SDB) have been linked to hypertension. However, the standard measure of SDB, the Apnoea Hypopnea Index (AHI), has not identified patients likely to experience large improvements in blood pressure with SDB treatment. METHODS: To use machine learning to select sleep and pulmonary measures associated with hypertension development when considered jointly, we applied feature screening followed by Elastic Net penalized regression in association with incident hypertension using a wide array of polysomnography measures, and lung function, derived for the Sleep Heart Health Study (SHHS). FINDINGS: At baseline, n=860 SHHS individuals with complete data were age 61 years, on average. Of these, 291 developed hypertension ~5 years later. A combination of pulmonary function and 18 sleep phenotypes predicted incident hypertension (OR=1.43, 95% confidence interval [1.14, 1.80] per 1 standard deviation (SD) of the phenotype), while the apnoea-hypopnea index (AHI) had low evidence of association with incident hypertension (OR =1.13, 95% confidence interval [0.97, 1.33] per 1 SD). In a generalization analysis in 923 individuals from the Multi-Ethnic Study of Atherosclerosis, aged 65 on average with 615 individuals with hypertension, the new phenotype was cross-sectionally associated with hypertension (OR=1.26, 95% CI [1.10, 1.45]). INTERPRETATION: A unique combination of sleep and pulmonary function measures better predicts hypertension compared to the AHI. The composite measure included indices capturing apnoea and hypopnea event durations, with shorter event lengths associated with increased risk of hypertension. FUNDING: This research was supported by National Heart, Lung, and Blood Institute (NHLBI) contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and by National Center for Advancing Translational Sciences grants UL1-TR- 000040, UL1-TR-001079, and UL1-TR-001420. The MESA Sleep ancillary study was supported by NHLBI grant HL-56984. Pulmonary phenotyping in MESA was funded by NHLBI grants R01-HL077612 and R01-HL093081. This work was supported by NHLBI grant R35HL135818 to Susan Redline.

8.
Hum Mol Genet ; 30(22): 2190-2204, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34165540

RESUMO

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P < 1 × 10-6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (P < 0.05 and consistent direction of effect, and P < 5 × 10-8 after meta-analysis), including two for WHRadjBMI (rs13301996, rs79478137); one for WCadjBMI (rs3168072) and one for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI, 10 for WCadjBMI and 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity susceptibility that may be ancestry-specific.

9.
Sci Rep ; 11(1): 13470, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188144

RESUMO

Arsenic exposure has been linked to poor pulmonary function, and inefficient arsenic metabolizers may be at increased risk. Dietary rice has recently been identified as a possible substantial route of exposure to arsenic, and it remains unknown whether it can provide a sufficient level of exposure to affect pulmonary function in inefficient metabolizers. Within 12,609 participants of HCHS/SOL, asthma diagnoses and spirometry-based measures of pulmonary function were assessed, and rice consumption was inferred from grain intake via a food frequency questionnaire. After stratifying by smoking history, the relationship between arsenic metabolism efficiency [percentages of inorganic arsenic (%iAs), monomethylarsenate (%MMA), and dimethylarsinate (%DMA) species in urine] and the measures of pulmonary function were estimated in a two-sample Mendelian randomization approach (genotype information from an Illumina HumanOmni2.5-8v1-1 array), focusing on participants with high inferred rice consumption. Among never-smoking high inferred consumers of rice (n = 1395), inefficient metabolism was associated with past asthma diagnosis and forced vital capacity below the lower limit of normal (LLN) (OR 1.40, p = 0.0212 and OR 1.42, p = 0.0072, respectively, for each percentage-point increase in %iAs; OR 1.26, p = 0.0240 and OR 1.24, p = 0.0193 for %MMA; OR 0.87, p = 0.0209 and OR 0.87, p = 0.0123 for the marker of efficient metabolism, %DMA). Among ever-smoking high inferred consumers of rice (n = 1127), inefficient metabolism was associated with peak expiratory flow below LLN (OR 1.54, p = 0.0108/percentage-point increase in %iAs, OR 1.37, p = 0.0097 for %MMA, and OR 0.83, p = 0.0093 for %DMA). Less efficient arsenic metabolism was associated with indicators of pulmonary dysfunction among those with high inferred rice consumption, suggesting that reductions in dietary arsenic could improve respiratory health.


Assuntos
Arsênio , Asma , Ácido Cacodílico , Hispano-Americanos , Oryza , Adulto , Arsênio/farmacocinética , Arsênio/toxicidade , Asma/induzido quimicamente , Asma/genética , Asma/fisiopatologia , Ácido Cacodílico/farmacocinética , Ácido Cacodílico/toxicidade , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Estados Unidos , Capacidade Vital
12.
Brief Bioinform ; 22(6)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34015820

RESUMO

Large datasets of hundreds to thousands of individuals measuring RNA-seq in observational studies are becoming available. Many popular software packages for analysis of RNA-seq data were constructed to study differences in expression signatures in an experimental design with well-defined conditions (exposures). In contrast, observational studies may have varying levels of confounding transcript-exposure associations; further, exposure measures may vary from discrete (exposed, yes/no) to continuous (levels of exposure), with non-normal distributions of exposure. We compare popular software for gene expression-DESeq2, edgeR and limma-as well as linear regression-based analyses for studying the association of continuous exposures with RNA-seq. We developed a computation pipeline that includes transformation, filtering and generation of empirical null distribution of association P-values, and we apply the pipeline to compute empirical P-values with multiple testing correction. We employ a resampling approach that allows for assessment of false positive detection across methods, power comparison and the computation of quantile empirical P-values. The results suggest that linear regression methods are substantially faster with better control of false detections than other methods, even with the resampling method to compute empirical P-values. We provide the proposed pipeline with fast algorithms in an R package Olivia, and implemented it to study the associations of measures of sleep disordered breathing with RNA-seq in peripheral blood mononuclear cells in participants from the Multi-Ethnic Study of Atherosclerosis.

13.
Neurotherapeutics ; 18(1): 228-243, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33829409

RESUMO

Epidemiological sleep research strives to identify the interactions and causal mechanisms by which sleep affects human health, and to design intervention strategies for improving sleep throughout the lifespan. These goals can be advanced by further focusing on the environmental and genetic etiology of sleep disorders, and by development of risk stratification algorithms, to identify people who are at risk or are affected by, sleep disorders. These studies rely on comprehensive sleep-related data which often contains complex multi-dimensional physiological and molecular measurements across multiple timepoints. Thus, sleep research is well-suited for the application of computational approaches that can handle high-dimensional data. Here, we survey recent advances in machine and deep learning together with the availability of large human cohort studies with sleep data that can jointly drive the next breakthroughs in the sleep-research field. We describe sleep-related data types and datasets, and present some of the tasks in the field that can be targets for algorithmic approaches, as well as the challenges and opportunities in pursuing them.

14.
Int J Obes (Lond) ; 45(7): 1532-1541, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33907307

RESUMO

BACKGROUND/OBJECTIVES: Neck circumference, an index of upper airway fat, has been suggested to be an important measure of body-fat distribution with unique associations with health outcomes such as obstructive sleep apnea and metabolic disease. This study aims to study the genetic bases of neck circumference. METHODS: We conducted a multi-ethnic genome-wide association study of neck circumference, adjusted and unadjusted for BMI, in up to 15,090 European Ancestry (EA) and African American (AA) individuals. Because sexually dimorphic associations have been observed for anthropometric traits, we conducted both sex-combined and sex-specific analysis. RESULTS: We identified rs227724 near the Noggin (NOG) gene as a possible quantitative locus for neck circumference in men (N = 8831, P = 1.74 × 10-9) but not in women (P = 0.08). The association was replicated in men (N = 1554, P = 0.045) in an independent dataset. This locus was previously reported to be associated with human height and with self-reported snoring. We also identified rs13087058 on chromosome 3 as a suggestive locus in sex-combined analysis (N = 15090, P = 2.94 × 10-7; replication P =0.049). This locus was also associated with electrocardiogram-assessed PR interval and is a cis-expression quantitative locus for the PDZ Domain-containing ring finger 2 (PDZRN3) gene. Both NOG and PDZRN3 interact with members of transforming growth factor-beta superfamily signaling proteins. CONCLUSIONS: Our study suggests that neck circumference may have unique genetic basis independent of BMI.

15.
Am J Respir Crit Care Med ; 203(12): 1546-1555, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33406013

RESUMO

Rationale: Randomized controlled trials have been unable to detect a cardiovascular benefit of continuous positive airway pressure in unselected patients with obstructive sleep apnea (OSA). We hypothesize that deleterious cardiovascular outcomes are concentrated in a subgroup of patients with a heightened pulse-rate response to apneas and hypopneas (ΔHR). Methods: We measured the ΔHR in the MESA (Multi-Ethnic Study of Atherosclerosis) (N = 1,395) and the SHHS (Sleep Heart Health Study) (N = 4,575). MESA data were used to determine the functional form of the association between the ΔHR and subclinical cardiovascular biomarkers, whereas primary analyses tested the association of the ΔHR with nonfatal or fatal cardiovascular disease (CVD) and all-cause mortality in longitudinal data from the SHHS. Measurements and Main Results: In the MESA, U-shaped relationships were observed between subclinical CVD biomarkers (coronary artery calcium, NT-proBNP [N-terminal prohormone BNP], and Framingham risk score) and the ΔHR; notably, a high ΔHR (upper quartile) was associated with elevated biomarker scores compared with a midrange ΔHR (25th-75th centiles). In the SHHS, individuals with a high ΔHR compared with a midrange ΔHR were at increased risk of nonfatal or fatal CVD and all-cause mortality (nonfatal adjusted hazard ratio [95% confidence interval (CI)], 1.60 [1.28-2.00]; fatal adjusted hazard ratio [95% CI], 1.68 [1.22-2.30]; all-cause adjusted hazard ratio [95% CI], 1.29 [1.07-1.55]). The risk associated with a high ΔHR was particularly high in those with a substantial hypoxic burden (nonfatal, 1.93 [1.36-2.73]; fatal, 3.50 [2.15-5.71]; all-cause, 1.84 [1.40-2.40]) and was exclusively observed in nonsleepy individuals. Conclusions: Individuals with OSA who demonstrate an elevated ΔHR are at increased risk of cardiovascular morbidity and mortality. This study identifies a prognostic biomarker for OSA that appears useful for risk stratification and patient selection for future clinical trials.


Assuntos
Biomarcadores , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Frequência Cardíaca , Prognóstico , Medição de Risco/métodos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade
16.
Sleep ; 44(3)2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33034629

RESUMO

Poor sleep quality can have harmful health consequences. Although many aspects of sleep are heritable, the understandings of genetic factors involved in its physiology remain limited. Here, we performed a genome-wide association study (GWAS) using the Pittsburgh Sleep Quality Index (PSQI) in a multi-ethnic discovery cohort (n = 2868) and found two novel genome-wide loci on chromosomes 2 and 7 associated with global sleep quality. A meta-analysis in 12 independent cohorts (100 000 individuals) replicated the association on chromosome 7 between NPY and MPP6. While NPY is an important sleep gene, we tested for an independent functional role of MPP6. Expression data showed an association of this locus with both NPY and MPP6 mRNA levels in brain tissues. Moreover, knockdown of an orthologue of MPP6 in Drosophila melanogaster sleep center neurons resulted in decreased sleep duration. With convergent evidence, we describe a new locus impacting human variability in sleep quality through known NPY and novel MPP6 sleep genes.


Assuntos
Drosophila melanogaster , Estudo de Associação Genômica Ampla , Animais , Grupos Étnicos , Predisposição Genética para Doença , Humanos , Proteínas de Membrana , Neurônios , Polimorfismo de Nucleotídeo Único/genética , Sono/genética
17.
Genet Epidemiol ; 45(1): 115-127, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33094516

RESUMO

Whole genome sequencing (WGS) and whole exome sequencing studies are used to test the association of rare genetic variants with health traits. Many existing WGS efforts now aggregate data from heterogeneous groups, for example, combining sets of individuals of European and African ancestries. We here investigate the statistical implications on rare variant association testing with a binary trait when combining together heterogeneous studies, defined as studies with potentially different disease proportion and different frequency of variant carriers. We study and compare in simulations the Type 1 error control and power of the naïve score test, the saddlepoint approximation to the score test, and the BinomiRare test in a range of settings, focusing on low numbers of variant carriers. We show that Type 1 error control and power patterns depend on both the number of carriers of the rare allele and on disease prevalence in each of the studies. We develop recommendations for association analysis of rare genetic variants. (1) The Score test is preferred when the case proportion in the sample is 50%. (2) Do not down-sample controls to balance case-control ratio, because it reduces power. Rather, use a test that controls the Type 1 error. (3) Conduct stratified analysis in parallel with combined analysis. Aggregated testing may have lower power when the variant effect size differs between strata.


Assuntos
Variação Genética , Modelos Genéticos , Estudos de Casos e Controles , Humanos , Fenótipo , Sequenciamento Completo do Genoma
18.
Alzheimers Dement ; 17(3): 466-474, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33155766

RESUMO

INTRODUCTION: Apolipoprotein E (APOE) alleles are associated with cognitive decline, mild cognitive impairment (MCI), and Alzheimer's disease in Whites, but have weaker and inconsistent effects reported in Latinos. We hypothesized that this heterogeneity is due to ancestry-specific genetic effects. METHODS: We investigated the associations of the APOE alleles with significant cognitive decline and MCI in 4183 Latinos, stratified by six Latino backgrounds, and explored whether the proportion of continental genetic ancestry (European, African, and Amerindian) modifies these associations. RESULTS: APOE ε4 was associated with an increased risk of significant cognitive decline (odds ratio [OR] = 1.15, P-value = 0.03), with the strongest association in Cubans (OR = 1.46, P-value = 0.007). APOE-ε2 was associated with decreased risk of MCI (OR = 0.37, P-value = 0.04) in Puerto Ricans. Amerindian genetic ancestry was found to protect from the risk conferred by APOE ε4 on significant cognitive decline. DISCUSSION: Results suggest that APOE alleles' effects on cognitive outcomes differ across six Latino backgrounds and are modified by continental genetic ancestry.

19.
Am J Respir Crit Care Med ; 203(3): 356-365, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758008

RESUMO

Rationale: Sleep disorders are associated with hypertension and diabetes, which are primary risk factors for cardiovascular diseases and mortality. It is important to understand these associations in Hispanic/Latino individuals, in whom cardiovascular death is the leading cause of mortality.Objectives: To investigate the prospective associations of sleep-disordered breathing (SDB) and insomnia with incident hypertension and diabetes among U.S. Hispanic/Latino people over 6 years of follow-up and to assess potential sex differences in these associations.Methods: Data from 11,623 Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos (visit 1, 2008-2011; visit 2, 2014-2017) were analyzed using survey logistic regression models, adjusting for potential confounders.Measurements and Main Results: SDB (apnea-hypopnea index of 5 or more) and insomnia (Women's Health Initiative Insomnia Rating Scale of 9 or more) were measured at baseline. Incident hypertension (stage 2 or greater) and diabetes were defined according to national guidelines. In the target population, 52.6% were women, with a mean age of 41.1 ± 14.9 years at baseline. SDB was associated with 1.54 higher adjusted odds of incident hypertension (95% confidence interval [CI], 1.18-2.00) and 1.33 higher odds of incident diabetes (95% CI, 1.05-1.67) compared with no SDB. Insomnia was associated with incident hypertension (odds ratio, 1.37; 95% CI, 1.11-1.69) but not with diabetes. The association between insomnia and incident hypertension was stronger among men than among women.Conclusions: SDB was associated with incident hypertension and diabetes. Insomnia was associated with incident hypertension. These findings support the importance of sleep disorders as modifiable targets for disease prevention and reduction.


Assuntos
Diabetes Mellitus/etiologia , Diabetes Mellitus/mortalidade , Hispano-Americanos/estatística & dados numéricos , Hipertensão/etiologia , Hipertensão/mortalidade , Síndromes da Apneia do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Adolescente , Adulto , Idoso , Fatores de Risco Cardiometabólico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Estados Unidos , Adulto Jovem
20.
J Sleep Res ; 30(2): e13033, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32198950

RESUMO

Discrepancies between actigraphic and self-reported sleep measures are common. Studies of people with insomnia, in whom both sleep disturbances and discrepancy are common, suggest disturbances and discrepancy reflect differences in the sleeping brain's activity measurable using spectral electroencephalogram (EEG). Disentangling effects of discrepancy and disturbance on sleep EEG could help target research on the consequences and treatments of different sleep phenotypes. We therefore categorized participants in a cohort study including 2,850 men (average age = 76 years, standard deviation = 5.5) into four groups using median splits on actigraphic and self-reported sleep efficiency (SE). We compared spectral power between these groups in 1-Hz bins up to 24 Hz. Compared with the concordant-high SE group: (a) the group with high actigraphic and low self-reported SE had higher spectral power from 11-15 Hz across the night; (b) both groups with low actigraphic SE had higher power across the 15-24 Hz range, predominantly in early cycles, and greater slow frequency power in later cycles. These findings suggest that perceived wakefulness undetected by actigraphy may result from or drive activity corresponding to spindles. We also found, consistent with hyperarousal models, that low SE detectable via actigraphy was related to higher frequency power in the beta range; actigraph-measured inefficiency was also associated with later slow oscillations, potentially representing attempts to dissipate homeostatic drive elevated from earlier hyperarousal. These distinct spectral EEG markers (of low SE measured with actigraphy vs. low perceived SE that is not captured by actigraphy) may have different causes or consequences.


Assuntos
Actigrafia/métodos , Eletroencefalografia/métodos , Transtornos do Sono-Vigília/diagnóstico , Sono/fisiologia , Estudos de Coortes , Humanos , Masculino , Autorrelato
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