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1.
Proc Natl Acad Sci U S A ; 119(35): e2206931119, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35994664

RESUMO

Sedentary behavior (SB) is associated with cardiometabolic disease and mortality, but its association with dementia is currently unclear. This study investigates whether SB is associated with incident dementia regardless of engagement in physical activity (PA). A total of 146,651 participants from the UK Biobank who were 60 years or older and did not have a diagnosis of dementia (mean [SD] age: 64.59 [2.84] years) were included. Self-reported leisure-time SBs were divided into two domains: time spent watching television (TV) or time spent using a computer. A total of 3,507 individuals were diagnosed with all-cause dementia over a mean follow-up of 11.87 (±1.17) years. In models adjusted for a wide range of covariates, including time spent in PA, time spent watching TV was associated with increased risk of incident dementia (HR [95% CI] = 1.24 [1.15 to 1.32]) and time spent using a computer was associated with decreased risk of incident dementia (HR [95% CI] = 0.85 [0.81 to 0.90]). In joint associations with PA, TV time and computer time remained significantly associated with dementia risk at all PA levels. Reducing time spent in cognitively passive SB (i.e., TV time) and increasing time spent in cognitively active SB (i.e., computer time) may be effective behavioral modification targets for reducing risk of dementia regardless of engagement in PA.


Assuntos
Computadores , Demência , Exercício Físico , Atividades de Lazer , Tempo de Tela , Comportamento Sedentário , Televisão , Idoso , Computadores/estatística & dados numéricos , Demência/epidemiologia , Demência/etiologia , Humanos , Incidência , Televisão/estatística & dados numéricos , Reino Unido
2.
Mol Psychiatry ; 28(11): 4594-4601, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37735503

RESUMO

Major depression (MD) is a serious psychiatric illness afflicting nearly 5% of the world's population. A large correlational literature suggests that loneliness is a prospective risk factor for MD; correlational assocations of this nature may be confounded for a variety of reasons. This report uses Mendelian Randomization (MR) to examine potentially causal associations between loneliness and MD. We report on analyses using summary statistics from three large genome wide association studies (GWAS). MR analyses were conducted using three independent sources of GWAS summary statistics. In the first set of analyses, we used available summary statistics from an extant GWAS of loneliness to predict MD risk. We used two sources of outcome data: the Psychiatric Genomics Consortium (PGC) meta-analysis of MD (PGC-MD; N = 142,646) and the Million Veteran Program (MVP-MD; N = 250,215). Finally, we reversed analyses using data from the MVP and PGC samples to identify risk variants for MD and used loneliness outcome data from UK Biobank. We find robust evidence for a bidirectional causal relationship between loneliness and MD, including between loneliness, depression cases status, and a continuous measure of depressive symptoms. The estimates remained significant across several sensitivity analyses, including models that account for horizontal pleiotropy. This paper provides the first genetically-informed evidence that reducing loneliness may play a causal role in decreasing risk for depressive illness, and these findings support efforts to reduce loneliness in order to prevent or ameliorate MD. Discussion focuses on the public health significance of these findings, especially in light of the SARS-CoV-2 pandemic.


Assuntos
Transtorno Depressivo Maior , Estudo de Associação Genômica Ampla , Humanos , Depressão/genética , Solidão , Análise da Randomização Mendeliana , Estudos Prospectivos , Transtorno Depressivo Maior/genética
3.
Environ Res ; 252(Pt 1): 118796, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38582433

RESUMO

BACKGROUND: Previous work has found climate change-induced weather variability is suspected to increase the transmission of enteric pathogens, including Campylobacter, a leading cause of bacterial gastroenteritis. While the relationship between extreme weather events and diarrheal diseases has been documented, the specific impact on Campylobacter infections remains underexplored. OBJECTIVE: To synthesize the peer-reviewed literature exploring the effect of weather variability on Campylobacter infections in humans. METHODS: The review included English language, peer-reviewed articles, published up to September 1, 2022 in PubMed, Embase, GEOBASE, Agriculture and Environmental Science Database, and CABI Global Health exploring the effect of an antecedent weather event on human enteric illness caused by Campylobacter (PROSPERO Protocol # 351884). We extracted study information including data sources, methods, summary measures, and effect sizes. Quality and weight of evidence reported was summarized and bias assessed for each article. RESULTS: After screening 278 articles, 47 articles (34 studies, 13 outbreak reports) were included in the evidence synthesis. Antecedent weather events included precipitation (n = 35), temperature (n = 30), relative humidity (n = 7), sunshine (n = 6), and El Niño and La Niña (n = 3). Reviewed studies demonstrated that increases in precipitation and temperature were correlated with Campylobacter infections under specific conditions, whereas low relative humidity and sunshine were negatively correlated. Articles estimating the effect of animal operations (n = 15) found presence and density of animal operations were significantly associated with infections. However, most of the included articles did not assess confounding by seasonality, presence of animal operations, or describe estimates of risk. DISCUSSION: This review explores what is known about the influence of weather events on Campylobacter and identifies previously underreported negative associations between low relative humidity and sunshine on Campylobacter infections. Future research should explore pathogen-specific estimates of risk, which can be used to influence public health strategies, improve source attribution and causal pathways, and project disease burden due to climate change.


Assuntos
Infecções por Campylobacter , Campylobacter , Tempo (Meteorologia) , Infecções por Campylobacter/epidemiologia , Humanos , Mudança Climática , Animais
4.
Hum Mol Genet ; 30(22): 2190-2204, 2021 11 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.


Assuntos
Adiposidade/genética , Distribuição da Gordura Corporal , Estudo de Associação Genômica Ampla , Hispânico ou Latino/genética , Característica Quantitativa Herdável , Alelos , Humanos , Polimorfismo de Nucleotídeo Único
5.
Ann Hepatol ; 28(5): 101120, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37271481

RESUMO

INTRODUCTION AND OBJECTIVES: Various studies have identified single-nucleotide polymorphisms (SNPs) associated with nonalcoholic fatty liver disease (NAFLD) and related traits, including ones located in or near the LYPLAL1, GCKR, PPP1R3B, TM6SF2, MBOAT7, and PNPLA3 genes. However, these SNPs were identified primarily in populations of European ancestry. This study examined the associations of these previously identified SNPs with hepatic steatosis in a sample of Mexican-origin adults living in Southern Arizona. MATERIALS AND METHODS: A total of 307 Mexican-origin adults between the ages of 18 and 64 with a body mass index (BMI) of 25 kg/m2 or higher were genotyped at the following SNPs: rs12137855 (LYPLAL1), rs1260326 (GCKR), rs4240624 (PPP1R3B), rs58542926 (TM6SF2), rs641738 (MBOAT7), and rs738409 (PNPLA3). Hepatic steatosis was assessed by transient elastography (FibroScan®) with controlled attenuation parameter. Regression models examined the association between each of the six SNPs and hepatic steatosis. BMI was examined as a potential modifier of the genetic associations. RESULTS: Participants were, on average, 45 years old and mostly female (63%) with an overall mean hepatic steatosis of 288.1 dB/m. Models showed no associations between LYPLAL1, GCKR, PPP1R3B, TM6SF2, or MBOAT7 and hepatic steatosis. Only PNPLA3 was statistically significantly associated with hepatic steatosis in both unadjusted and adjusted models (p<0.01). There was no effect modification observed with BMI. CONCLUSIONS: SNPs associated with NAFLD in populations of European descent did not strongly contribute to hepatic steatosis in individuals of Mexican-origin, except for rs738409 (PNPLA3). Further efforts are necessary to explore additional SNPs that may be associated with NAFLD in this high-risk population.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Adulto , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Predisposição Genética para Doença , Genótipo , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Fígado
6.
JAMA ; 330(10): 934-940, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698563

RESUMO

Importance: Sedentary behavior is associated with cardiometabolic disease and mortality, but its association with dementia is unclear. Objective: To investigate whether accelerometer-assessed sedentary behavior is associated with incident dementia. Design, Setting, and Participants: A retrospective study of prospectively collected data from the UK Biobank including 49 841 adults aged 60 years or older without a diagnosis of dementia at the time of wearing the wrist accelerometer and living in England, Scotland, or Wales. Follow-up began at the time of wearing the accelerometer (February 2013 to December 2015) and continued until September 2021 in England, July 2021 in Scotland, and February 2018 in Wales. Exposures: Mean daily sedentary behavior time (included in the primary analysis) and mean daily sedentary bout length, maximum daily sedentary bout length, and mean number of daily sedentary bouts (included in the secondary analyses) were derived from a machine learning-based analysis of 1 week of wrist-worn accelerometer data. Main Outcome and Measures: Incident all-cause dementia diagnosis from inpatient hospital records and death registry data. Cox proportional hazard models with linear and cubic spline terms were used to assess associations. Results: A total of 49 841 older adults (mean age, 67.19 [SD, 4.29] years; 54.7% were female) were followed up for a mean of 6.72 years (SD, 0.95 years). During this time, 414 individuals were diagnosed with incident all-cause dementia. In the fully adjusted models, there was a significant nonlinear association between time spent in sedentary behavior and incident dementia. Relative to a median of 9.27 hours/d for sedentary behavior, the hazard ratios (HRs) for dementia were 1.08 (95% CI, 1.04-1.12, P < .001) for 10 hours/d, 1.63 (95% CI, 1.35-1.97, P < .001) for 12 hours/d, and 3.21 (95% CI, 2.05-5.04, P < .001) for 15 hours/d. The adjusted incidence rate of dementia per 1000 person-years was 7.49 (95% CI, 7.48-7.49) for 9.27 hours/d of sedentary behavior, 8.06 (95% CI, 7.76-8.36) for 10 hours/d, 12.00 (95% CI, 10.00-14.36) for 12 hours/d, and 22.74 (95% CI, 14.92-34.11) for 15 hours/d. Mean daily sedentary bout length (HR, 1.53 [95% CI, 1.03-2.27], P = .04 and 0.65 [95% CI, 0.04-1.57] more dementia cases per 1000 person-years for a 1-hour increase from the mean of 0.48 hours) and maximum daily sedentary bout length (HR, 1.15 [95% CI, 1.02-1.31], P = .02 and 0.19 [95% CI, 0.02-0.38] more dementia cases per 1000 person-years for a 1-hour increase from the mean of 1.95 hours) were significantly associated with higher risk of incident dementia. The number of sedentary bouts per day was not associated with higher risk of incident dementia (HR, 1.00 [95% CI, 0.99-1.01], P = .89). In the sensitivity analyses, after adjustment for time spent in sedentary behavior, the mean daily sedentary bout length and the maximum daily sedentary bout length were no longer significantly associated with incident dementia. Conclusions and Relevance: Among older adults, more time spent in sedentary behaviors was significantly associated with higher incidence of all-cause dementia. Future research is needed to determine whether the association between sedentary behavior and risk of dementia is causal.


Assuntos
Demência , Comportamento Sedentário , Idoso , Feminino , Humanos , Masculino , Demência/epidemiologia , Demência/etiologia , Inglaterra , Estudos Retrospectivos , Acelerometria , Incidência , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Sistema de Registros/estatística & dados numéricos
7.
Environ Res ; 209: 112895, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35149105

RESUMO

BACKGROUND: Air pollution may cause inflammatory and oxidative stress damage to the brain, leading to neurodegenerative disease. The association between air pollution and dementia, and modification by apolipoprotein E genotype 4 (APOE-ε4) has yet to be fully investigated. OBJECTIVES: To examine associations of air pollution with three types of incident dementias (Alzheimer's disease (AD), frontotemporal dementia (FTD), and vascular dementia (VAD)), and their potential modification by APOE-ε4 genotype. METHODS: The UK Biobank enrolled >500,000 participants (2006-2010) with ongoing follow-up. We used annual averages of air pollution (PM2.5, PM10, PM2.5-10, PM2.5absorbance, NO2, NOX) for 2010 scaled to interquartile ranges (IQR). We included individuals aged ≥60 years, with no dementia diagnosis prior to January 1, 2010. Time to incident dementia and follow-up time were reported from baseline (January 01, 2010) to last censor event (death, last hospitalization, or loss to follow-up). Cox proportional hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated to estimate the association of air pollutants and incident dementia, and modification of these associations by APOE-ε4. RESULTS: Our sample included 187,194 individuals (including N = 680 AD, N = 377 VAD, N = 63 FTD) with a mean follow-up of 7.04 years. We observed consistent associations of PM2.5 with greater risk of all-cause dementia (HR = 1.17, 95% CI: 1.10, 1.24) and AD (HR = 1.17, 95% CI: 1.06, 1.29). NO2 was also associated with greater risk of any incident dementia (HR = 1.18, 95% CI: 1.10, 1.25), AD (HR = 1.15, 95% CI: 1.04, 1.28) and VAD (HR = 1.18, 95% CI: 1.03, 1.35). APOE-ε4 did not modify the association between any air pollutants and dementia. DISCUSSION: PM2.5 and NO2 levels were associated with several types of dementia, and these associations were not modified by APOE-ε4. Findings from the UK Biobank support and extend to other epidemiological evidence for the potential association of air pollutants with detrimental brain health during aging.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença de Alzheimer , Doenças Neurodegenerativas , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Bancos de Espécimes Biológicos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Pessoa de Meia-Idade , Material Particulado/análise , Material Particulado/toxicidade , Reino Unido/epidemiologia
8.
Nutr Metab Cardiovasc Dis ; 32(4): 1027-1034, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35168826

RESUMO

BACKGROUND AND AIMS: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits. METHODS AND RESULTS: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple loci reached genome-wide levels of significance (N = 145-333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10-8). We sought replication of these four loci in an independent set of seven trait-specific GWAS meta-analyses. GRB14-COBLL1 showed the most consistent replication, revealing nominally significant associations (P < 0.05) with all traits except DBP. CONCLUSIONS: Our analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets.


Assuntos
Estudo de Associação Genômica Ampla , Hipertensão , Adiposidade/genética , HDL-Colesterol , Loci Gênicos , Humanos , Hipertensão/diagnóstico , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Relação Cintura-Quadril
9.
J Public Health (Oxf) ; 44(3): 532-540, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-33837421

RESUMO

BACKGROUND: Although chronic kidney disease (CKD) affects 15% of the United States (US) population, <10% of the US CKD population is aware of their disease. This is significant as untreated CKD can progress to end-stage renal disease which would require dialysis or transplantation. This study aimed to provide updated information regarding US CKD unawareness. METHODS: Data from the 1999-2014 National Health and Nutrition Examination Survey (NHANES) were used (n = 38 474); response rate > 70%. CKD self-report and lab-confirmed CKD were used to assess CKD unawareness. Adjusted logistic regression models examined association between unawareness and patient characteristics. RESULTS: In individuals with lab-confirmed CKD (n = 7137, 14.3%), 91.5% answered 'no' to self-report question; in those without CKD, 1.1% answered 'yes' to self-report question. In those with lab-confirmed CKD, in the adjusted models, increased age [odds ratio (ORs), 1.03 (95%CI, 1.02-1.04)] and female sex [OR, 1.37 (95%CI, 1.08-1.72)] were statistically significantly associated with greater odds of being unaware of CKD. CONCLUSION: These findings demonstrated high unawareness of disease status as there was a discrepancy between respondents' self-reported CKD diagnosis and lab-confirmed CKD. Older individuals and women may be more unaware of their CKD; these groups should be queried about reasons for increased unawareness.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Conscientização , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Inquéritos Nutricionais , Razão de Chances , Insuficiência Renal Crônica/epidemiologia , Estados Unidos/epidemiologia
10.
Hum Hered ; 86(1-4): 21-27, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34749354

RESUMO

INTRODUCTION: Liver disease accounts for approximately 2 million deaths per year worldwide. The majority of liver diseases are due to complications of cirrhosis, viral hepatitis, and hepatocellular carcinoma. Increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may indicate liver disease. Moreover, there are additional noninvasive liver fibrosis indices that help to estimate liver damage, including AST-to-ALT ratio, AST-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and nonalcoholic fatty liver disease (NAFLD) fibrosis score. The aims of the present study were to (1) perform an association analysis of the patatin-like phospholipase domain containing 3 (PNPLA3) I148M (rs738409) variant with ALT, AST, and various liver fibrosis indices, and (2) determine whether there are gender-related differences in these associations. METHODS: We obtained demographic, anthropometric, and metabolic phenotypes from Latino adult participants (n = 503, 64% female, 36.4 ± 0.5 years) from the Arizona Insulin Resistance (AIR) registry. SNP genotyping of I148M was performed using the TaqMan allelic discrimination assay. We used linear regression for the association analyses of the genotypes with ALT, AST, and the various liver fibrosis indices. We included genotype, age, body mass index, and alcohol status in the linear regression model. RESULTS: The variant I148M was in Hardy-Weinberg equilibrium, with genotype distribution: non-risk CC 118, heterozygous CG 246, and risk GG 139. The G allele was significantly associated with increased ALT and AST levels (p = 7.8 × 10-7 and p = 9.7 × 10-6, respectively). Moreover, we showed that the G allele was significantly associated with higher APRI (p = 3.7 × 10-7) and FIB-4 score (p = 4.1 × 10-3). When we analyzed the data by gender, we observed similar significant trends for ALT, AST, and APRI (all, p < 0.01). In females, the G allele was significantly associated with increased FIB-4 score (p = 6.9 × 10-3), which was not observed in the males (p > 0.05). There was no association of the I148M variant with AST/ALT ratio nor NAFLD risk score, whether analyzed in all adults or by gender. DISCUSSION/CONCLUSION: Our findings provide additional evidence of an association of PNPLA3 I148M with several liver disease biomarkers in male and female Latinos residing in the Southwest of the United States.


Assuntos
Lipase , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Feminino , Predisposição Genética para Doença , Hispânico ou Latino/genética , Humanos , Lipase/genética , Masculino , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único/genética
11.
Genet Epidemiol ; 44(3): 248-260, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31879980

RESUMO

Logistic regression is the primary analysis tool for binary traits in genome-wide association studies (GWAS). Multinomial regression extends logistic regression to multiple categories. However, many phenotypes more naturally take ordered, discrete values. Examples include (a) subtypes defined from multiple sources of clinical information and (b) derived phenotypes generated by specific phenotyping algorithms for electronic health records (EHR). GWAS of ordinal traits have been problematic. Dichotomizing can lead to a range of arbitrary cutoff values, generating inconsistent, hard to interpret results. Using multinomial regression ignores trait value hierarchy and potentially loses power. Treating ordinal data as quantitative can lead to misleading inference. To address these issues, we analyze ordinal traits with an ordered, multinomial model. This approach increases power and leads to more interpretable results. We derive efficient algorithms for computing test statistics, making ordinal trait GWAS computationally practical for Biobank scale data. Our method is available as a Julia package OrdinalGWAS.jl. Application to a COPDGene study confirms previously found signals based on binary case-control status, but with more significance. Additionally, we demonstrate the capability of our package to run on UK Biobank data by analyzing hypertension as an ordinal trait.


Assuntos
Bancos de Espécimes Biológicos , Estudo de Associação Genômica Ampla , Algoritmos , Estudos de Casos e Controles , Simulação por Computador , Humanos , Hipertensão/genética , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Análise de Regressão , Testes de Função Respiratória
12.
Br J Cancer ; 124(7): 1330-1338, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33510439

RESUMO

BACKGROUND: We conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat. METHODS: Common genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios. We analysed the effect of these instrumental variables in a colorectal cancer genome-wide association study comprising 31,197 cases and 61,770 controls of European ancestry by applying two-sample and multivariable MR study designs. RESULTS: We found decreased colorectal cancer risk for genetically represented measures of MVPA and AMPA that were additional to effects mediated through genetic measures of obesity. Odds ratio and 95% confidence interval (CI) per standard deviation increase in MVPA and AMPA was 0.56 (0.31, 1.01) and 0.60 (0.41, 0.88), respectively. No association has been found between sedentary time and colorectal cancer risk. The proportion of effect mediated through BMI was 2% (95% CI: 0, 14) and 32% (95% CI: 12, 46) for MVPA and AMPA, respectively. CONCLUSION: These findings provide strong evidence to reinforce public health measures on preventing colorectal cancer that promote PA at a population level regardless of body fatness.


Assuntos
Adiposidade , Índice de Massa Corporal , Neoplasias Colorretais/epidemiologia , Exercício Físico , Análise da Randomização Mendeliana/métodos , Obesidade/complicações , Comportamento Sedentário , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Europa (Continente) , Estudo de Associação Genômica Ampla , Humanos , Obesidade/epidemiologia , Obesidade/genética , Prognóstico , Fatores de Risco
13.
Prev Chronic Dis ; 18: E104, 2021 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-34941480

RESUMO

INTRODUCTION: National obesity prevention strategies may benefit from precision health approaches involving diverse participants in population health studies. We used cohort data from the National Institutes of Health All of Us Research Program (All of Us) Researcher Workbench to estimate population-level obesity prevalence. METHODS: To estimate state-level obesity prevalence we used data from physical measurements made during All of Us enrollment visits and data from participant electronic health records (EHRs) where available. Prevalence estimates were calculated and mapped by state for 2 categories of body mass index (BMI) (kg/m2): obesity (BMI >30) and severe obesity (BMI >35). We calculated and mapped prevalence by state, excluding states with fewer than 100 All of Us participants. RESULTS: Data on height and weight were available for 244,504 All of Us participants from 33 states, and corresponding EHR data were available for 88,840 of these participants. The median and IQR of BMI taken from physical measurements data was 28.4 (24.4- 33.7) and 28.5 (24.5-33.6) from EHR data, where available. Overall obesity prevalence based on physical measurements data was 41.5% (95% CI, 41.3%-41.7%); prevalence of severe obesity was 20.7% (95% CI, 20.6-20.9), with large geographic variations observed across states. Prevalence estimates from states with greater numbers of All of Us participants were more similar to national population-based estimates than states with fewer participants. CONCLUSION: All of Us participants had a high prevalence of obesity, with state-level geographic variation mirroring national trends. The diversity among All of Us participants may support future investigations on obesity prevention and treatment in diverse populations.


Assuntos
Obesidade Mórbida , Saúde da População , Índice de Massa Corporal , Humanos , Obesidade/epidemiologia , Prevalência , Estados Unidos/epidemiologia
14.
Malar J ; 19(1): 272, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727452

RESUMO

BACKGROUND: Alternative long-lasting insecticidal net (LLIN) use for purposes other than sleeping protection from mosquitoes is widely debated as a limitation to successful malaria control efforts, yet rarely rigorously studied. METHODS: A cross-sectional survey of 1217 households in an epidemic highland site and an endemic lowland site in western Kenya collected information on alternative use in three ways: direct observations, participant self-report, and participant reporting of community-level practices. LLIN misuse was defined as use of an intact net for alternative purposes and repurposing as alternatively using an old or damaged net. Associations between households with observed repurposed nets and universal access and household net use were examined. RESULTS: Households describe repurposing nets when they are torn and/or old. Repurposed nets were observed in 8.1% (52/643) highlands households and 33.0% (184/574) lowlands households. Repurposed nets served as chicken coops (33% highlands, 20% lowlands), fences (37% highlands, 25% lowlands), tree covers (22% lowlands), curtains (3% highlands), covering bathrooms (1.5% highlands, 9% lowlands), and washing sponges (13% lowlands). No association was found between repurposing and universal access or household net use. Misuse was rare. Of 379 repurposed nets, 4 (1.06%) were in good condition with no holes. Of 1,758 active nets, 13 (0.74%) were misused. CONCLUSIONS: Alternative net use in this study involved repurposing rather than misuse. Repurposing was not detrimental to malaria prevention efforts in these communities. Standardized measurement of alternative net use should be used to better understand the practice and its potential impact on the success of malaria interventions.


Assuntos
Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Controle de Mosquitos/estatística & dados numéricos , Propriedade , Estudos Transversais , Características da Família , Quênia , Malária/prevenção & controle , Controle de Mosquitos/organização & administração , Propriedade/estatística & dados numéricos
15.
Environ Res ; 185: 109364, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32247148

RESUMO

Air pollution has consistently been associated with cardiometabolic outcomes, although associations with obesity have only been recently reported. Studies of air pollution and adiposity have mostly relied on body mass index (BMI) rather than body fat percentage (BF%), and most have not accounted for noise as a possible confounder. Additionally, it is unknown whether genetic predisposition for obesity increases susceptibility to the obesogenic effects of air pollution. To help fill these gaps, we used the UK Biobank, a large, prospective cohort study in the United Kingdom, to explore the relationship between air pollution and adiposity, and modification by a polygenic risk score for BMI. We used 2010 annual averages of air pollution estimates from land use regression (NO2, NOX, PM2.5, PM2.5absorbance, PM2.5-10, PM10), traffic intensity (TI), inverse distance to road (IDTR), along with examiner-measured BMI, waist-hip-ratio (WHR), and impedance measures of BF%, which were collected at enrollment (2006-2010, n = 473,026) and at follow-up (2012-2013, n = 19,518). We estimated associations of air pollution with BMI, WHR, and BF% at enrollment and follow-up, and with obesity, abdominal obesity, and BF%-obesity at enrollment and follow-up. We used linear and logistic regression and controlled for noise and other covariates. We also assessed interactions of air pollution with a polygenic risk score for BMI. On average, participants at enrollment were 56 years of age, 54% were female, and 32% had completed college or a higher degree. Almost all participants (~95%) were white. All air pollution measures except IDTR were positively associated with at least one continuous measure of adiposity at enrollment. However, NO2 was negatively associated with BMI but positively associated with WHR at enrollment, and IDTR was also negatively associated with BMI. At follow-up (controlling for enrollment adiposity), we observed positive associations for PM2.5-10 with BMI, PM10 with BF%, and TI with BF% and BMI. Associations were similar for binary measures of adiposity, with minor differences for some pollutants. Associations of NOX, NO2, PM2.5absorbance, PM2.5 and PM10, with BMI at enrollment, but not at follow-up, were stronger among individuals with higher BMI polygenic risk scores (interaction p <0.05). In this large, prospective cohort, air pollution was associated with several measures of adiposity at enrollment and follow-up, and associations with adiposity at enrollment were modified by a polygenic risk score for obesity.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Bancos de Espécimes Biológicos , Tecido Adiposo/química , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/genética , Material Particulado , Estudos Prospectivos , Reino Unido/epidemiologia
16.
Malar J ; 18(1): 274, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412865

RESUMO

BACKGROUND: Insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are effective for malaria prevention and are designed to provide nearly 5 years of mosquito protection. However, many ITNs and LLINs become damaged and ineffective for mosquito bite prevention within 1 to 2 years in field conditions. Non-adherence to recommended bed net care and repair practices may partially explain this shortened net longevity. METHODS: Using data from a cross-sectional study, a net care adherence score was developed and adherence to net care practices described from two regions of western Kenya. Relationships between attitudes and environmental factors that influence net longevity were measured with adherence to bed net care practices. RESULTS: While overall care practices are highly adherent particularly in the highlands, practices related to daily storage, washing frequency, and drying location need improvement in the lowlands. Seventy-seven percent of nets in the lowlands were washed < 3 months prior to the survey compared to 23% of nets in the highlands. More nets were dried in the sun in the lowlands (32% of nets) compared to the highlands (4% of nets). Different elements of care are influenced by various malaria attitudes and environmental factors, highlighting the complexity of factors associated with net care. For example, households that learned about net care from community events, that share a sleeping structure with animals, and that have nets used by adult males tend to adhere to washing frequency recommendations. CONCLUSIONS: In western Kenya, many nets are cared for in accordance to recommended practices, particularly in the highlands sites. In the lowlands, demonstrating methods at community events to tie nets up during the day coupled with messaging to emphasize infrequent washing and drying nets in the shade may be an appropriate intervention. As illustrated by differences between the highlands and lowlands sites in the present study, should interventions to improve adherence to bed net care practices be necessary, they should be context-specific.


Assuntos
Mordeduras e Picadas de Insetos/prevenção & controle , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/prevenção & controle , Controle de Mosquitos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anopheles , Criança , Pré-Escolar , Estudos Transversais , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Quênia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
JAMA ; 331(5): 443, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319334
18.
Int J Obes (Lond) ; 42(6): 1161-1176, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29899525

RESUMO

BACKGROUND/OBJECTIVES: Physical activity (PA) protects against a wide range of diseases. Habitual PA appears to be heritable, motivating the search for specific genetic variants that may inform efforts to promote PA and target the best type of PA for each individual. SUBJECTS/METHODS: We used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (nmax = 377,234) and two measures based on wrist-worn accelerometry data (nmax = 91,084). We examined genetic correlations of PA with other traits and diseases, as well as tissue-specific gene expression patterns. With data from the Atherosclerosis Risk in Communities (ARIC; n = 8,556) study, we performed a meta-analysis of our top hits for moderate-to-vigorous PA (MVPA). RESULTS: We identified ten loci across all PA measures that were significant in both a basic and a fully adjusted model (p < 5 × 10-9). Upon meta-analysis of the nine top hits for MVPA with results from ARIC, eight were genome-wide significant. Interestingly, among these, the rs429358 variant in the APOE gene was the most strongly associated with MVPA, whereby the allele associated with higher Alzheimer's risk was associated with greater MVPA. However, we were not able to rule out possible selection bias underlying this result. Variants in CADM2, a gene previously implicated in obesity, risk-taking behavior and other traits, were found to be associated with habitual PA. We also identified three loci consistently associated (p < 5 × 10-5) with PA across both self-report and accelerometry, including CADM2. We found genetic correlations of PA with educational attainment, chronotype, psychiatric traits, and obesity-related traits. Tissue enrichment analyses implicate the brain and pituitary gland as locations where PA-associated loci may exert their actions. CONCLUSIONS: These results provide new insight into the genetic basis of habitual PA, and the genetic links connecting PA with other traits and diseases.


Assuntos
Apolipoproteínas E/genética , Bancos de Espécimes Biológicos , Moléculas de Adesão Celular/genética , Exercício Físico , Predisposição Genética para Doença , Adulto , Idoso , Exercício Físico/fisiologia , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Reino Unido/epidemiologia
19.
PLoS Genet ; 11(5): e1005204, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26020539

RESUMO

Elevated plasma triglyceride (TG) levels are an established risk factor for type-2 diabetes (T2D). However, recent studies have hinted at the possibility that genetic risk for TG may paradoxically protect against T2D. In this study, we examined the association of genetic risk for TG with incident T2D, and the interaction of baseline TG with TG genetic risk on incident T2D in 13,247 European-Americans (EA) and 3,238 African-Americans (AA) from three prospective cohort studies. A TG genetic risk score (GRS) was calculated based on 31 validated single nucleotide polymorphisms (SNPs). We considered several baseline covariates, including body- mass index (BMI) and lipid traits. Among EA and AA, we find, as expected, that baseline levels of TG are strongly positively associated with incident T2D (p<2 x 10-(10)). However, the TG GRS is negatively associated with T2D (p=0.013), upon adjusting for only race, in the full dataset. Upon additionally adjusting for age, sex, BMI, high-density lipoprotein cholesterol and TG, the TG GRS is significantly and negatively associated with T2D incidence (p=7.0 x 10(-8)), with similar trends among both EA and AA. No single SNP appears to be driving this association. We also find a significant statistical interaction of the TG GRS with TG (pi(nteraction) = 3.3 x 10-(4)), whereby the association of TG with incident T2D is strongest among those with low genetic risk for TG. Further research is needed to understand the likely pleiotropic mechanisms underlying these findings, and to clarify the causal relationship between T2D and TG.


Assuntos
Diabetes Mellitus Tipo 2/genética , Estudos de Associação Genética , Metabolismo dos Lipídeos/genética , Triglicerídeos/sangue , Negro ou Afro-Americano/genética , Alelos , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Triglicerídeos/genética , População Branca/genética
20.
Rheumatol Int ; 36(2): 263-70, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26427508

RESUMO

We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk of incident gout. We measured the incidence of gout and associated comorbidities using the original and offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the eight SNPs. Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P = 6.12E-03). We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk of gout may involve complex interplay between genes and environment.


Assuntos
Índice de Massa Corporal , Interação Gene-Ambiente , Gota/genética , Hiperuricemia/genética , Nefropatias/epidemiologia , Polimorfismo de Nucleotídeo Único , Ácido Úrico/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Comorbidade , Feminino , Frequência do Gene , Loci Gênicos , Predisposição Genética para Doença , Gota/sangue , Gota/diagnóstico , Gota/epidemiologia , Humanos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Incidência , Nefropatias/diagnóstico , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Modelos Genéticos , Modelos Estatísticos , Fenótipo , Fatores de Risco , Fatores Sexuais
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