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1.
Am J Hum Genet ; 105(5): 1057-1068, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31668705

RESUMO

Average arterial oxyhemoglobin saturation during sleep (AvSpO2S) is a clinically relevant measure of physiological stress associated with sleep-disordered breathing, and this measure predicts incident cardiovascular disease and mortality. Using high-depth whole-genome sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) project and focusing on genes with linkage evidence on chromosome 8p23,1,2 we observed that six coding and 51 noncoding variants in a gene that encodes the GTPase-activating protein (DLC1) are significantly associated with AvSpO2S and replicated in independent subjects. The combined DLC1 association evidence of discovery and replication cohorts reaches genome-wide significance in European Americans (p = 7.9 × 10-7). A risk score for these variants, built on an independent dataset, explains 0.97% of the AvSpO2S variation and contributes to the linkage evidence. The 51 noncoding variants are enriched in regulatory features in a human lung fibroblast cell line and contribute to DLC1 expression variation. Mendelian randomization analysis using these variants indicates a significant causal effect of DLC1 expression in fibroblasts on AvSpO2S. Multiple sources of information, including genetic variants, gene expression, and methylation, consistently suggest that DLC1 is a gene associated with AvSpO2S.

2.
Sci Rep ; 9(1): 9439, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263163

RESUMO

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10-8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

3.
PLoS Genet ; 15(4): e1007739, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30990817

RESUMO

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.


Assuntos
Hexoquinase/genética , Subunidade alfa de Receptor de Interleucina-18/genética , Oxiemoglobinas/metabolismo , Sono/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular Neuronais/genética , Biologia Computacional , Proteínas da Matriz Extracelular/genética , Feminino , Redes Reguladoras de Genes , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Hipóxia/sangue , Hipóxia/genética , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas do Tecido Nervoso/genética , Oxigênio/sangue , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Serina Endopeptidases/genética , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/genética , Adulto Jovem
4.
CMAJ ; 190(23): E710-E717, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891475

RESUMO

BACKGROUND: Understanding the complex interaction of risk factors that increase the likelihood of developing common diseases is challenging. The Canadian Partnership for Tomorrow Project (CPTP) is a prospective cohort study created as a population-health research platform for assessing the effect of genetics, behaviour, family health history and environment (among other factors) on chronic diseases. METHODS: Volunteer participants were recruited from the general Canadian population for a confederation of 5 regional cohorts. Participants were enrolled in the study and core information obtained using 2 approaches: attendance at a study assessment centre for all study measures (questionnaire, venous blood sample and physical measurements) or completion of the core questionnaire (online or paper), with later collection of other study measures where possible. Physical measurements included height, weight, percentage body fat and blood pressure. Participants consented to passive follow-up through linkage with administrative health databases and active follow-up through recontact. All participant data across the 5 regional cohorts were harmonized. RESULTS: A total of 307 017 participants aged 30-74 from 8 provinces were recruited. More than half provided a venous blood sample and/or other biological sample, and 33% completed physical measurements. A total of 709 harmonized variables were created; almost 25% are available for all participants and 60% for at least 220 000 participants. INTERPRETATION: Primary recruitment for the CPTP is complete, and data and biosamples are available to Canadian and international researchers through a data-access process. The CPTP will support research into how modifiable risk factors, genetics and the environment interact to affect the development of cancer and other chronic diseases, ultimately contributing evidence to reduce the global burden of chronic disease.

6.
Respirology ; 23(1): 18-27, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29113020

RESUMO

Obstructive sleep apnoea (OSA) is a common chronic disease and is associated with high social and economic costs. OSA is heritable, and there is evidence of both direct genetic contributions to OSA susceptibility and indirect contributions via 'intermediate' phenotypes such as obesity, craniofacial structure, neurological control of upper airway muscles and of sleep and circadian rhythm. Investigation of the genetics of OSA is an important research area and may lead to improved understanding of disease aetiology, pathogenesis, adverse health consequences and new preventive strategies and treatments. Genetic studies of OSA have lagged behind other chronic diseases; however recent gene discovery efforts have been successful in finding genetic loci contributing to OSA-associated intermediate phenotypes. Nevertheless, many of the seminal questions relating to the genetic epidemiology of OSA and associated factors remain unanswered. This paper reviews the current state of knowledge of the genetics of OSA, with a focus on genomic approaches to understanding sleep apnoea.


Assuntos
Genômica , Apneia Obstrutiva do Sono/genética , Face/anatomia & histologia , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Obesidade/complicações , Obesidade/genética , Fenótipo , Crânio/anatomia & histologia , Apneia Obstrutiva do Sono/complicações
7.
Am J Respir Cell Mol Biol ; 58(3): 391-401, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29077507

RESUMO

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas/genética , Apneia Obstrutiva do Sono/genética , Sono REM/fisiologia , Fatores de Transcrição/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidiletanolamina N-Metiltransferase/genética , Caracteres Sexuais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteínas ras/genética
8.
Am J Respir Crit Care Med ; 196(11): 1456-1462, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28743190

RESUMO

RATIONALE: Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. OBJECTIVES: To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease. METHODS: This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone. Renal function and adverse renal events were compared between the CPAP (n = 102) and usual care (n = 98) groups. Glomerular filtration rate was estimated at randomization and at the end of follow-up, and the urinary albumin-to-creatinine ratio was measured at study exit. MEASUREMENTS AND MAIN RESULTS: In 200 substudy participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h; mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m2), the median (interquartile range) changes in estimated glomerular filtration rate (ml/min/1.73 m2/yr) were -1.64 (-3.45 to -0.740) in the CPAP group and -2.30 (-4.53 to -0.71) in the usual care group (P = 0.21) after a median of 4.4 years. There were no between-group differences in end-of-study urinary albumin-to-creatinine ratio or in the occurrence of serious renal or urinary adverse events during the trial. The level of CPAP adherence did not influence the findings. CONCLUSIONS: CPAP treatment of OSA in patients with cardiovascular disease does not alter renal function or the occurrence of renal adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT00738179).


Assuntos
Doenças Cardiovasculares/complicações , Pressão Positiva Contínua nas Vias Aéreas/métodos , Rim/fisiopatologia , Insuficiência Renal Crônica/complicações , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Idoso , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Testes de Função Renal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia
9.
Sci Rep ; 7(1): 1648, 2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28490744

RESUMO

Precision medicine approaches rely on obtaining precise knowledge of the true state of health of an individual patient, which results from a combination of their genetic risks and environmental exposures. This approach is currently limited by the lack of effective and efficient non-invasive medical tests to define the full range of phenotypic variation associated with individual health. Such knowledge is critical for improved early intervention, for better treatment decisions, and for ameliorating the steadily worsening epidemic of chronic disease. We present proof-of-concept experiments to demonstrate how routinely acquired cross-sectional CT imaging may be used to predict patient longevity as a proxy for overall individual health and disease status using computer image analysis techniques. Despite the limitations of a modest dataset and the use of off-the-shelf machine learning methods, our results are comparable to previous 'manual' clinical methods for longevity prediction. This work demonstrates that radiomics techniques can be used to extract biomarkers relevant to one of the most widely used outcomes in epidemiological and clinical research - mortality, and that deep learning with convolutional neural networks can be usefully applied to radiomics research. Computer image analysis applied to routinely collected medical images offers substantial potential to enhance precision medicine initiatives.

10.
BMC Genet ; 17(1): 116, 2016 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-27514831

RESUMO

BACKGROUND: Genome-wide association studies of Single Nucleotide Polymorphisms (SNPs) have identified 55 SNPs associated with lung function. However, little is known about the effect of copy number variants (CNVs) on lung function, although CNVs represent a significant proportion of human genetic polymorphism. To assess the effect of CNVs on lung function quantitative traits, we measured copy number at 2788 previously characterised, common copy number variable regions in 6 independent cohorts (n = 24,237) using intensity data from SNP genotyping experiments. We developed a pipeline for genome-wide association analysis and meta-analysis of CNV genotypes measured across multiple studies using SNP genotype array intensity data from different platform technologies. We then undertook cohort-level genome-wide association studies of CNV with lung function in a subset of 4 cohorts (n < =12,403) with lung function measurements and meta-analysed the results. Follow-up was undertaken for CNVs which were well tagged by SNPs, in up to 146,871 individuals. RESULTS: We generated robust copy number calls for 1962 out of 2788 (70 %) known CNV regions genome-wide, with 1103 measured with compatible class frequencies in at least 2 cohorts. We report a novel CNV association (discovery P = 0.0007) with Forced Vital Capacity (FVC) downstream of BANP on chromosome 16 that shows evidence of replication by a tag SNP in two independent studies (replication P = 0.004). In addition, we provide suggestive evidence (discovery P = 0.0002) for a role of complex copy number variation at a previously reported lung function locus, containing the rootletin gene CROCC, that is not tagged by SNPs. CONCLUSIONS: We demonstrate how common CNV regions can be reliably and consistently called across cohorts, using an existing calling algorithm and rigorous quality control steps, using SNP genotyping array intensity data. Although many common biallelic CNV regions were well-tagged by common SNPs, we also identified associations with untagged mulitallelic CNV regions thereby illustrating the potential of our approach to identify some of the missing heritability of complex traits.


Assuntos
Proteínas de Ciclo Celular/genética , Variações do Número de Cópias de DNA , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla , Proteínas Nucleares/genética , Capacidade Vital/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Genótipo , Humanos , Pulmão , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Vigilância da População , Testes de Função Respiratória , Adulto Jovem
11.
Circ Cardiovasc Genet ; 9(3): 266-278, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26969751

RESUMO

BACKGROUND: Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence. METHODS AND RESULTS: Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4-7 years), puberty (8-12 years), and postpuberty (13-20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5'-C-phosphate-G-3' methylation site) during prepuberty (P=2.86×10(-8)) and rs872256 during puberty (P=8.67×10(-9)). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10(-3). Using a P value threshold of <5×10(-3), we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms. CONCLUSIONS: Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.


Assuntos
Pressão Sanguínea/genética , Loci Gênicos , Hipertensão/genética , Cadeias alfa de Integrinas/genética , Adolescente , Fatores Etários , Criança , Pré-Escolar , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/diagnóstico , Hipertensão/etnologia , Hipertensão/fisiopatologia , Masculino , Epidemiologia Molecular , Fenótipo , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Adulto Jovem
12.
J Clin Sleep Med ; 11(10): 1091-9, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26285117

RESUMO

STUDY OBJECTIVE: To investigate whether low levels of physical activity were associated with an increased occurrence of obstructive sleep apnea (OSA), OSA-related symptoms, and cardiometabolic risk. METHODS: A case-control study design was used. OSA cases were patients referred to a sleep clinic for suspected OSA (n = 2,340). Controls comprised participants from the Busselton community (n = 1,931). Exercise and occupational activity were derived from questionnaire data. Associations were modelled using logistic and linear regression and adjusted for confounders. RESULTS: In comparison with moderate exercise, the high, low, and nil exercise groups had an odds ratio (OR) for moderate-severe OSA of 0.6 (95% CI 0.5-0.8), 1.6 (95% CI 1.2-2.0), and 2.7 (95% CI 1.9-3.7), respectively. Relative to men in heavy activity occupations, men in medium, light and sedentary occupations had an OR for moderate-severe OSA of 1.7 (95% CI 1.1-2.5), 2.1 (95% CI 1.4-3.2), and 1.8 (95% CI 1.2-2.8), respectively. Relative to women in medium activity occupations, women in light and sedentary occupations had an OR for moderate-severe OSA of 4.2 (95% CI 2.6-7.2) and 3.5 (2.0-6.0). OSA patients who adequately exercised had lower: levels of doctor-diagnosed depression (p = 0.047); symptoms of fatigue (p < 0.0001); systolic (p = 0.015) and diastolic blood pressure (p = 0.015); and C-reactive protein (CRP) (p = 0.003). CONCLUSIONS: Low levels of physical activity were associated with moderate-severe OSA. Exercise in individuals with OSA is associated with lower levels of depression, fatigue, blood pressure and CRP.


Assuntos
Comportamento Sedentário , Apneia Obstrutiva do Sono/epidemiologia , Austrália/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polissonografia , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários
13.
Sci Rep ; 5: 11610, 2015 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-26158911

RESUMO

Studies have shown that natural environments can enhance health and here we build upon that work by examining the associations between comprehensive greenspace metrics and health. We focused on a large urban population center (Toronto, Canada) and related the two domains by combining high-resolution satellite imagery and individual tree data from Toronto with questionnaire-based self-reports of general health perception, cardio-metabolic conditions and mental illnesses from the Ontario Health Study. Results from multiple regressions and multivariate canonical correlation analyses suggest that people who live in neighborhoods with a higher density of trees on their streets report significantly higher health perception and significantly less cardio-metabolic conditions (controlling for socio-economic and demographic factors). We find that having 10 more trees in a city block, on average, improves health perception in ways comparable to an increase in annual personal income of $10,000 and moving to a neighborhood with $10,000 higher median income or being 7 years younger. We also find that having 11 more trees in a city block, on average, decreases cardio-metabolic conditions in ways comparable to an increase in annual personal income of $20,000 and moving to a neighborhood with $20,000 higher median income or being 1.4 years younger.


Assuntos
Nível de Saúde , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Canadá , Feminino , Coração/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Características de Residência , Autorrelato , Fatores Sexuais , Fatores Socioeconômicos , Inquéritos e Questionários , População Urbana , Adulto Jovem
15.
Int J Epidemiol ; 44(2): 700-12, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25953783

RESUMO

BACKGROUND: Several studies have investigated the effect of known adult body mass index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in childhood. There has been no genome-wide association study (GWAS) of BMI trajectories over childhood. METHODS: We conducted a GWAS meta-analysis of BMI trajectories from 1 to 17 years of age in 9377 children (77,967 measurements) from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western Australian Pregnancy Cohort (Raine) Study. Genome-wide significant loci were examined in a further 3918 individuals (48,530 measurements) from Northern Finland. Linear mixed effects models with smoothing splines were used in each cohort for longitudinal modelling of BMI. RESULTS: A novel SNP, downstream from the FAM120AOS gene on chromosome 9, was detected in the meta-analysis of ALSPAC and Raine. This association was driven by a difference in BMI at 8 years (T allele of rs944990 increased BMI; PSNP = 1.52 × 10(-8)), with a modest association with change in BMI over time (PWald(Change) = 0.006). Three known adult BMI-associated loci (FTO, MC4R and ADCY3) and one childhood obesity locus (OLFM4) reached genome-wide significance (PWald < 1.13 × 10(-8)) with BMI at 8 years and/or change over time. CONCLUSIONS: This GWAS of BMI trajectories over childhood identified a novel locus that warrants further investigation. We also observed genome-wide significance with previously established obesity loci, making the novel observation that these loci affected both the level and the rate of change in BMI. We have demonstrated that the use of repeated measures data can increase power to allow detection of genetic loci with smaller sample sizes.


Assuntos
Índice de Massa Corporal , Obesidade Pediátrica/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas de Ligação a RNA/genética , Adenilil Ciclases/genética , Adolescente , Estatura/genética , Peso Corporal/genética , Criança , Pré-Escolar , Cromossomos Humanos Par 9/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Fator Estimulador de Colônias de Granulócitos/genética , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto/genética , Receptor Tipo 4 de Melanocortina/genética
16.
J Clin Sleep Med ; 11(9): 1029-38, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25902824

RESUMO

STUDY OBJECTIVES: To determine prevalence of depressive symptoms in obstructive sleep apnea (OSA) and the impact of OSA treatment on depression scores. METHODS: Consecutive new patients referred for investigation of suspected OSA were approached. Consenting patients completed a patient health questionnaire (PHQ-9) for depressive symptoms when attending for laboratory polysomnography. Those with moderate/severe (apneahypopnea index [AHI] ≥ 15 events/h) and/or symptomatic mild OSA (AHI 5-14.99 events/h) were offered continuous positive airway pressure (CPAP) therapy. PHQ-9 was repeated after 3 months of CPAP with compliance recorded. Of a maximum PHQ-9 score of 27, a cut point ≥ 10 (PHQ-9 ≥ 10) was used to indicate presence of clinically significant depressive symptoms. RESULTS: A total of 426 participants (243 males) were recruited. Mean ± standard deviation body mass index (BMI) was 32.1 ± 7.1 kg/m2 and AHI 33.6 ± 28.9 events/h. PHQ-9 was 10.5 ± 6.1 and independently related to AHI (p < 0.001) and BMI (p < 0.001). In those without OSA, PHQ-9 ≥ 10 was more common in women, but no gender difference was evident with OSA. Of 293 patients offered CPAP, 228 were compliant (mean nightly use > 5 h) over 3 months of therapy. In them, with therapy, AHI decreased from 46.7 ± 27.4 to 6.5 ± 1.6 events/h, PHQ-9 from 11.3 ± 6.1 to 3.7 ± 2.9 and PHQ-9 ≥ 10 from 74.6% to 3.9% (p < 0.001 in each case). Magnitude of change in PHQ-9 was similar in men and women. Antidepressant use was constant throughout. CONCLUSIONS: Depressive symptoms are common in OSA and related to its severity. They improve markedly with CPAP, implying a relationship to untreated OSA.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia , Adulto , Comorbidade , Feminino , Humanos , Masculino , Polissonografia , Prevalência , Índice de Gravidade de Doença , Fatores Sexuais , Apneia Obstrutiva do Sono/psicologia , Inquéritos e Questionários , Resultado do Tratamento
17.
J Clin Sleep Med ; 11(4): 433-44, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25580606

RESUMO

STUDY OBJECTIVES: We hypothesized that a dual-channel portable monitor (PM) device could accurately identify patients who have a high pretest probability of obstructive sleep apnea (OSA), and we evaluated factors that may contribute to variability between PM and polysomnography (PSG) results. METHODS: Consecutive clinic patients (N = 104) with possible OSA completed a home PM study, a PM study simultaneous with laboratory PSG, and a second home PM study. Uniform data analysis methods were applied to both PM and PSG data. Primary outcomes of interest were the positive likelihood ratio (LR+) and sensitivity of the PM device to "rule-in" OSA, defined as an apnea-hypopnea index (AHI) ≥ 5 events/h on PSG. Effects of different test environment and study nights, and order of study and analysis methods (manual compared to automated) on PM diagnostic accuracy were assessed. RESULTS: The PM has adequate LR+ (4.8), sensitivity (80%), and specificity (83%) for detecting OSA in the unattended home setting when benchmarked against laboratory PSG, with better LR+ (> 5) and specificity (100%) and unchanged sensitivity (80%) in the simultaneous laboratory comparison. There were no significant night-night (all p > 0.10) or study order effects (home or laboratory first, p = 0.08) on AHI measures. Manual PM data review improved case finding accuracy, although this was not statistically significant (all p > 0.07). Misclassification was more frequent where OSA was mild. CONCLUSIONS: Overall performance of the PM device is consistent with current recommended criteria for an "acceptable" device to confidently "rule-in" OSA (AHI ≥ 5 events/h) in a high pretest probability clinic population. Our data support the utility of simple two-channel diagnostic devices to confirm the diagnosis of OSA in the home environment. COMMENTARY: A commentary on this article appears in this issue on page 411.


Assuntos
Monitorização Fisiológica/métodos , Apneia Obstrutiva do Sono/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Polissonografia , Reprodutibilidade dos Testes , Apneia Obstrutiva do Sono/fisiopatologia
18.
Eur J Clin Invest ; 44(9): 883-91, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25041535

RESUMO

BACKGROUND: The burden of chronic disease is projected to assume crisis proportions in most parts of the world by the middle of the century, focusing attention on the need for preventive interventions. We identify and review published research on primary prevention individual-level interventions in current practice and describe and discuss the limitations of the current evidence. The report facilitates prioritizing a research agenda for potential interventions that might be investigated within cohort studies. MATERIALS AND METHODS: This study is a rapid review. Computerized database searches (PubMed and EMBASE) were performed in October 2012 to identify articles on primary prevention interventions that are directed at the individual level. Potentially, relevant International Agency of Research on Cancer handbooks and monographs were also reviewed. The review includes articles reported in English on the efficacy or effectiveness of a preventive intervention in an adult population. It excludes articles on alcohol or tobacco smoking. RESULTS: Many chronic disease interventions directed at individuals report a protective effect in the short term and some evidence for the efficacy of chemoprevention in chronic disease prevention exists. Evidence these effects persist in the longer term is inconsistent. CONCLUSIONS: There are currently only limited evidence-based preventions for most chronic diseases, for which a summary is available in Table A1 (see Appendix B). Most individual-level intervention research studies have been conducted using case-control designs and some small, randomized studies. There are fewer impediments to lifestyle modifications when compared to prevention using chemoprevention and vaccination or other methods of prevention of persistent infection.


Assuntos
Doença Crônica/prevenção & controle , Anti-Inflamatórios não Esteroides/uso terapêutico , Dieta , Exercício , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori , Hepatite B Crônica/prevenção & controle , Humanos , Minerais/uso terapêutico , Infecções por Papillomavirus/prevenção & controle , Polimedicação , Comportamento de Redução do Risco , Vitaminas/uso terapêutico
19.
Can J Public Health ; 105(2): e150-3, 2014 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-24886853

RESUMO

The Population Studies Research Network of Cancer Care Ontario hosted a strategic planning workshop to establish an agenda for a prevention intervention research program in Ontario, including priority topics for investigation and design considerations. The two-day workshop included: presentations on background papers developed to facilitate participants' preparation for and discussions in the workshop; keynote presentations on intervention research concerning primary prevention of chronic diseases, design and study implementation considerations; a dedicated session on critical and creative thinking to stimulate participation and discussion topics; break out groups to identify, discuss and present study ideas, designs, implementation considerations; and a consensus process to discuss and identify recommendations for research priorities and next steps. The retreat yielded the following recommendations: 1) develop an intervention research agenda that includes working with existing large-scale cohorts; 2) develop an intervention research agenda that includes novel research designs that could target individuals or groups; and 3) develop an intervention research agenda in which studies collect data on costs, define stakeholders, and ensure clear strategies for stakeholder engagement and knowledge transfer. The Population Studies Research Network will develop options from these recommendations and release a call for proposals in 2014 for intervention research pilot projects that reflect these recommendations. Pilot projects will be evaluated based on their fit with the retreat's recommendations, and their potential to scale up to full studies and application in practice.


Assuntos
Pesquisa Biomédica/métodos , Doença Crônica/prevenção & controle , Projetos de Pesquisa , Congressos como Assunto , Humanos , Ontário
20.
J Am Acad Child Adolesc Psychiatry ; 53(6): 667-676.e7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24839885

RESUMO

OBJECTIVE: Preschool internalizing problems (INT) are highly heritable and moderately genetically stable from childhood into adulthood. Gene-finding studies are scarce. In this study, the influence of genome-wide measured single nucleotide polymorphisms (SNPs) was investigated in 3 cohorts (total N = 4,596 children) in which INT was assessed with the same instrument, the Child Behavior Checklist (CBCL). METHOD: First, genome-wide association (GWA) results were used for density estimation and genome-wide complex trait analysis (GCTA) to calculate the variance explained by all SNPs. Next, a fixed-effect inverse variance meta-analysis of the 3 GWA analyses was carried out. Finally, the overlap in results with prior GWA studies of childhood and adulthood psychiatric disorders and treatment responses was tested by examining whether SNPs associated with these traits jointly showed a significant signal for INT. RESULTS: Genome-wide SNPs explained 13% to 43% of the total variance. This indicates that the genetic architecture of INT mirrors the polygenic model underlying adult psychiatric traits. The meta-analysis did not yield a genome-wide significant signal but was suggestive for the PCSK2 gene located on chromosome 20p12.1. SNPs associated with other psychiatric disorders appeared to be enriched for signals with INT (λ = 1.26, p < .03). CONCLUSION: Our study provides evidence that INT is influenced by many common genetic variants, each with a very small effect, and that, even as early as age 3, genetic variants influencing INT overlap with variants that play a role in childhood and adulthood psychiatric disorders.


Assuntos
Transtornos do Comportamento Infantil/genética , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Polimorfismo de Nucleotídeo Único/genética , Pró-Proteína Convertase 2/genética , Sistema de Registros/estatística & dados numéricos , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino
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