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2.
Hum Genet ; 139(1): 23-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31030318

RESUMO

Replicable genetic association signals have consistently been found through genome-wide association studies in recent years. The recent dramatic expansion of study sizes improves power of estimation of effect sizes, genomic prediction, causal inference, and polygenic selection, but it simultaneously increases susceptibility of these methods to bias due to subtle population structure. Standard methods using genetic principal components to correct for structure might not always be appropriate and we use a simulation study to illustrate when correction might be ineffective for avoiding biases. New methods such as trans-ethnic modeling and chromosome painting allow for a richer understanding of the relationship between traits and population structure. We illustrate the arguments using real examples (stroke and educational attainment) and provide a more nuanced understanding of population structure, which is set to be revisited as a critical aspect of future analyses in genetic epidemiology. We also make simple recommendations for how problems can be avoided in the future. Our results have particular importance for the implementation of GWAS meta-analysis, for prediction of traits, and for causal inference.


Assuntos
Algoritmos , Bancos de Espécimes Biológicos/estatística & dados numéricos , Genética Populacional , Estudo de Associação Genômica Ampla , Herança Multifatorial , Humanos , Polimorfismo de Nucleotídeo Único
3.
JAMA ; 322(22): 2191-2202, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31821430

RESUMO

Importance: Hereditary transthyretin (TTR) amyloid cardiomyopathy (hATTR-CM) due to the TTR V122I variant is an autosomal-dominant disorder that causes heart failure in elderly individuals of African ancestry. The clinical associations of carrying the variant, its effect in other African ancestry populations including Hispanic/Latino individuals, and the rates of achieving a clinical diagnosis in carriers are unknown. Objective: To assess the association between the TTR V122I variant and heart failure and identify rates of hATTR-CM diagnosis among carriers with heart failure. Design, Setting, and Participants: Cross-sectional analysis of carriers and noncarriers of TTR V122I of African ancestry aged 50 years or older enrolled in the Penn Medicine Biobank between 2008 and 2017 using electronic health record data from 1996 to 2017. Case-control study in participants of African and Hispanic/Latino ancestry with and without heart failure in the Mount Sinai BioMe Biobank enrolled between 2007 and 2015 using electronic health record data from 2007 to 2018. Exposures: TTR V122I carrier status. Main Outcomes and Measures: The primary outcome was prevalent heart failure. The rate of diagnosis with hATTR-CM among TTR V122I carriers with heart failure was measured. Results: The cross-sectional cohort included 3724 individuals of African ancestry with a median age of 64 years (interquartile range, 57-71); 1755 (47%) were male, 2896 (78%) had a diagnosis of hypertension, and 753 (20%) had a history of myocardial infarction or coronary revascularization. There were 116 TTR V122I carriers (3.1%); 1121 participants (30%) had heart failure. The case-control study consisted of 2307 individuals of African ancestry and 3663 Hispanic/Latino individuals; the median age was 73 years (interquartile range, 68-80), 2271 (38%) were male, 4709 (79%) had a diagnosis of hypertension, and 1008 (17%) had a history of myocardial infarction or coronary revascularization. There were 1376 cases of heart failure. TTR V122I was associated with higher rates of heart failure (cross-sectional cohort: n = 51/116 TTR V122I carriers [44%], n = 1070/3608 noncarriers [30%], adjusted odds ratio, 1.7 [95% CI, 1.2-2.4], P = .006; case-control study: n = 36/1376 heart failure cases [2.6%], n = 82/4594 controls [1.8%], adjusted odds ratio, 1.8 [95% CI, 1.2-2.7], P = .008). Ten of 92 TTR V122I carriers with heart failure (11%) were diagnosed as having hATTR-CM; the median time from onset of symptoms to clinical diagnosis was 3 years. Conclusions and Relevance: Among individuals of African or Hispanic/Latino ancestry enrolled in 2 academic medical center-based biobanks, the TTR V122I genetic variant was significantly associated with heart failure.


Assuntos
Afro-Americanos/genética , Neuropatias Amiloides Familiares/genética , Insuficiência Cardíaca/genética , Hispano-Americanos/genética , Pré-Albumina/genética , Centros Médicos Acadêmicos , Idoso , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/etnologia , Bancos de Espécimes Biológicos , Estudos de Casos e Controles , Estudos Transversais , Feminino , Variação Genética , Insuficiência Cardíaca/etnologia , Humanos , Masculino , Pessoa de Meia-Idade
4.
Nat Genet ; 51(12): 1749-1755, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31768069

RESUMO

The genome-wide association study (GWAS) has been widely used as an experimental design to detect associations between genetic variants and a phenotype. Two major confounding factors, population stratification and relatedness, could potentially lead to inflated GWAS test statistics and hence to spurious associations. Mixed linear model (MLM)-based approaches can be used to account for sample structure. However, genome-wide association (GWA) analyses in biobank samples such as the UK Biobank (UKB) often exceed the capability of most existing MLM-based tools especially if the number of traits is large. Here, we develop an MLM-based tool (fastGWA) that controls for population stratification by principal components and for relatedness by a sparse genetic relationship matrix for GWA analyses of biobank-scale data. We demonstrate by extensive simulations that fastGWA is reliable, robust and highly resource-efficient. We then apply fastGWA to 2,173 traits on array-genotyped and imputed samples from 456,422 individuals and to 2,048 traits on whole-exome-sequenced samples from 46,191 individuals in the UKB.


Assuntos
Estudo de Associação Genômica Ampla/estatística & dados numéricos , Modelos Lineares , Bancos de Espécimes Biológicos , Índice de Massa Corporal , Interpretação Estatística de Dados , Humanos , Desequilíbrio de Ligação , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Software , Reino Unido , Sequenciamento Completo do Exoma
5.
PLoS Genet ; 15(10): e1008353, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31671092

RESUMO

Mendelian randomization (MR) is an established approach to evaluate the effect of an exposure on an outcome. The gene-by-environment (GxE) study design can be used to determine whether the genetic instrument affects the outcome through pathways other than via the exposure of interest (horizontal pleiotropy). MR phenome-wide association studies (MR-pheWAS) search for the effects of an exposure, and can be conducted in UK Biobank using the PHESANT package. In this proof-of-principle study, we introduce the novel GxE MR-pheWAS approach, that combines MR-pheWAS with the use of GxE interactions. This method aims to identify the presence of effects of an exposure while simultaneously investigating horizontal pleiotropy. We systematically test for the presence of causal effects of smoking heaviness-stratifying on smoking status (ever versus never)-as an exemplar. If a genetic variant is associated with smoking heaviness (but not smoking initiation), and this variant affects an outcome (at least partially) via tobacco intake, we would expect the effect of the variant on the outcome to differ in ever versus never smokers. We used PHESANT to test for the presence of effects of smoking heaviness, instrumented by genetic variant rs16969968, among never and ever smokers respectively, in UK Biobank. We ranked results by the strength of interaction between ever and never smokers. We replicated previously established effects of smoking heaviness, including detrimental effects on lung function. Novel results included a detrimental effect of heavier smoking on facial aging. We have demonstrated how GxE MR-pheWAS can be used to identify potential effects of an exposure, while simultaneously assessing whether results may be biased by horizontal pleiotropy.


Assuntos
Fumar Cigarros/epidemiologia , Biologia Computacional/métodos , Análise da Randomização Mendeliana/métodos , Envelhecimento da Pele/efeitos dos fármacos , Bancos de Espécimes Biológicos , Fumar Cigarros/efeitos adversos , Fumar Cigarros/genética , Interação Gene-Ambiente , Pleiotropia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudo de Prova de Conceito , Reino Unido/epidemiologia
6.
Nat Med ; 25(11): 1753-1760, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700174

RESUMO

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment.


Assuntos
Doenças Cardiovasculares/diagnóstico , Taxa de Filtração Glomerular/fisiologia , Falência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/diagnóstico , Adulto , Idoso , Albuminúria/complicações , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Albuminúria/urina , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Biomarcadores/urina , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Creatinina/metabolismo , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
7.
BMC Bioinformatics ; 20(1): 542, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675914

RESUMO

BACKGROUND: In biological experiments, comprehensive experimental metadata tracking - which comprises experiment, reagent, and protocol annotation with controlled vocabulary from established ontologies - remains a challenge, especially when the experiment involves multiple laboratory scientists who execute different steps of the protocol. Here we describe Annot, a novel web application designed to provide a flexible solution for this task. RESULTS: Annot enforces the use of controlled vocabulary for sample and reagent annotation while enabling robust investigation, study, and protocol tracking. The cornerstone of Annot's implementation is a json syntax-compatible file format, which can capture detailed metadata for all aspects of complex biological experiments. Data stored in this json file format can easily be ported into spreadsheet or data frame files that can be loaded into R ( https://www.r-project.org/ ) or Pandas, Python's data analysis library ( https://pandas.pydata.org/ ). Annot is implemented in Python3 and utilizes the Django web framework, Postgresql, Nginx, and Debian. It is deployed via Docker and supports all major browsers. CONCLUSIONS: Annot offers a robust solution to annotate samples, reagents, and experimental protocols for established assays where multiple laboratory scientists are involved. Further, it provides a framework to store and retrieve metadata for data analysis and integration, and therefore ensures that data generated in different experiments can be integrated and jointly analyzed. This type of solution to metadata tracking can enhance the utility of large-scale datasets, which we demonstrate here with a large-scale microenvironment microarray study.


Assuntos
Biologia Computacional/métodos , Curadoria de Dados/métodos , Indicadores e Reagentes/provisão & distribução , Metadados , Bancos de Espécimes Biológicos/estatística & dados numéricos , Software , Vocabulário Controlado
9.
Life Sci ; 238: 116894, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626789

RESUMO

AIMS: MicroRNAs (miRs) and their importance in development, normal physiology, and disease have become increasingly recognized. Our laboratory is interested in miR-29 and its effects on lung development. These studies set out to identify optimal conditions for the measurement of miR-29 in heparinized, biobanked samples and to compare isoform expression patterns. MATERIALS AND METHODS: The efficiency of three distinct heparinases were tested using reverse transcriptase polymerase chain reaction (RT-PCR): recombinant F. Heparinum heparinase I; recombinant P. heparinus heparinase II; recombinant P. heparinus heparinase III; and heparinase I (B. efferthii-derived). The effects of freeze/thaws, and the relative expression of different miR-29 isoforms were also assessed using RT-PCR. KEY FINDINGS: Our investigations determined that heparinase 1 (recombinant F. Heparinum) and 2 (recombinant P. heparinus) at 1 or 2 h incubation efficiently neutralized heparin activity and prevented interference with the PCR. Also, a single freeze/thaw did not affect the measurement of miR-29-3p but multiple freeze/thaw cycles decreased the measureable miR levels. Finally, the -3p strand was most abundantly expressed in all three isoforms in both human and mouse plasma. SIGNIFICANCE: Our findings illustrate that specific conditions need to be optimized for the particular miR and the type of sample being tested.


Assuntos
Bancos de Espécimes Biológicos/normas , Heparina/sangue , MicroRNAs/sangue , Animais , Estudos de Coortes , Flavobacterium/enzimologia , Heparina Liase/metabolismo , Humanos , Lactente , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Polissacarídeo-Liase/metabolismo , Proteínas Recombinantes/metabolismo
10.
Hum Genet ; 138(11-12): 1287-1299, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31620872

RESUMO

Biobank operations started officially in Finland in 2013 when the Biobank Act defining and regulating biobank operations came into force. Since then, ten biobanks have been established and they have started to collect new prospective samples with broad consent. The main corpus of biobank samples, however, consists of approximately 10 million "legacy samples". These are old diagnostic or research samples that were transferred to biobanks in accordance with the Biobank Act. The focus of this article is on ambiguities concerning these legacy samples and their transfer in terms of legality, human rights, autonomy, and social sustainability. We analyse the Finnish biobank operations in the context of international regulation, such as the European Convention of Human Rights, the Oviedo Convention, European Charter of Fundamental Rights, the GDPR, and EU Clinical Trials Regulation, and show that the practice of using legacy samples is at times problematic in relation to this regulatory framework. We argue that the prevailing interpretations of these regulations as translated into the Finnish biobank practices undermine the autonomy of individuals by not giving individuals a right to consent or an actionable right to opt-out of the transfer of these legacy samples to the biobank. This is due to the fact that individuals are not given effective notification of such transfers. Thus, issues regarding the legal status of the biobank samples and the social sustainability of biobank operations remain a challenge for biobanks in Finland despite governmental efforts to create pioneering, comprehensive, and enabling legislation.


Assuntos
Bancos de Espécimes Biológicos/legislação & jurisprudência , Bancos de Espécimes Biológicos/normas , Pesquisa Biomédica/ética , Manejo de Espécimes/ética , Manejo de Espécimes/normas , Finlândia , Humanos , Estudos Prospectivos
11.
Malar J ; 18(1): 336, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578142

RESUMO

BACKGROUND: Rapid diagnostic tests (RDTs) have been described as a source of genetic material to analyse malaria parasites in proof-of-concept studies. The increasing use of RDTs (e.g., in focal or mass screening and treatment campaigns) makes this approach particularly attractive for large-scale investigations of parasite populations. In this study, the complexity of Plasmodium falciparum infections, parasite load and chloroquine resistance transporter gene mutations were investigated in DNA samples extracted from positive RDTs, obtained in a routine setting and archived at ambient temperature. METHODS: A total of 669 archived RDTs collected from malaria cases in urban, semi-urban and rural areas of central Gabon were used for P. falciparum DNA extraction. Performance of RDTs as a source of DNA for PCR was determined using: (i) amplification of a single copy merozoite surface protein 1 (msp1) gene followed by highly sensitive and automated capillary electrophoresis; (ii) genotyping of the pfcrt gene locus 72-76 using haplotype-specific-probe-based real-time PCR to characterize chloroquine resistance; and, (iii) real-time PCR targeting 18S genes to detect and quantify Plasmodium parasites. RESULTS: Out of the 669 archived RDTs, amplification of P. falciparum nucleic materials had a success rate of 97% for 18S real-time PCR, and 88% for the msp1 gene. The multiplicity of infections (MOI) of the whole population was 2.6 (95% CI 2.5-2.8). The highest number of alleles detected in one infection was 11. The MOI decreased with increasing age (ß = - 0.0046, p = 0.02) and residence in Lambaréné was associated with smaller MOIs (p < 0.001). The overall prevalence of mutations associated with chloroquine resistance was 78.5% and was not associated with age. In Lambaréné, prevalence of chloroquine resistance was lower compared to rural Moyen-Ogooué (ß = - 0.809, p-value = 0.011). CONCLUSION: RDT is a reliable source of DNA for P. falciparum detection and genotyping assays. Furthermore, the increasing use of RDTs allows them to be an alternative source of DNA for large-scale genetic epidemiological studies. Parasite populations in the study area are highly diverse and prevalence of chloroquine-resistant P. falciparum remains high, especially in rural areas.


Assuntos
Bancos de Espécimes Biológicos , DNA de Protozoário/isolamento & purificação , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Adolescente , Adulto , Temperatura Corporal , Criança , Pré-Escolar , Cloroquina/farmacologia , DNA de Protozoário/genética , Resistência a Medicamentos/genética , Feminino , Gabão , Genótipo , Humanos , Malária Falciparum/sangue , Malária Falciparum/diagnóstico , Masculino , Proteínas de Membrana Transportadoras/genética , Proteína 1 de Superfície de Merozoito/genética , Técnicas de Diagnóstico Molecular , Parasitemia , Plasmodium falciparum/efeitos dos fármacos , Estudos Retrospectivos , Adulto Jovem
12.
Adv Exp Med Biol ; 1200: 413-463, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31471805

RESUMO

Amphibians have experienced a catastrophic decline since the 1980s driven by disease, habitat loss, and impacts of invasive species and face ongoing threats from climate change. About 40% of extant amphibians are under threat of extinction and about 200 species have disappeared completely. Reproductive technologies and biobanking of cryopreserved materials offer technologies that could increase the efficiency and effectiveness of conservation programs involving management of captive breeding and wild populations through reduced costs, better genetic management and reduced risk of species extinctions. However, there are relatively few examples of applications of these technologies in practice in on-the-ground conservation programs, and no example that we know of where genetic diversity has been restored to a threatened amphibian species in captive breeding or in wild populations using cryopreserved genetic material. This gap in the application of technology to conservation programs needs to be addressed if assisted reproductive technologies (ARTs) and biobanking are to realise their potential in amphibian conservation. We review successful technologies including non-invasive gamete collection, IVF and sperm cryopreservation that work well enough to be applied to many current conservation programs. We consider new advances in technology (vitrification and laser warming) of cryopreservation of aquatic embryos of fish and some marine invertebrates that may help us to overcome factors limiting amphibian oocyte and embryo cryopreservation. Finally, we address two case studies that illustrate the urgent need and the opportunity to implement immediately ARTs, cryopreservation and biobanking to amphibian conservation. These are (1) managing the biosecurity (disease risk) of the frogs of New Guinea which are currently free of chytridiomycosis, but are at high risk (2) the Sehuencas water frog of Bolivia, which until recently had only one known surviving male.


Assuntos
Anfíbios , Bancos de Espécimes Biológicos , Conservação dos Recursos Naturais , Técnicas de Reprodução Assistida/veterinária , Animais , Espécies em Perigo de Extinção
13.
Nat Med ; 25(9): 1442-1452, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31477907

RESUMO

Our understanding of how the gut microbiome interacts with its human host has been restrained by limited access to longitudinal datasets to examine stability and dynamics, and by having only a few isolates to test mechanistic hypotheses. Here, we present the Broad Institute-OpenBiome Microbiome Library (BIO-ML), a comprehensive collection of 7,758 gut bacterial isolates paired with 3,632 genome sequences and longitudinal multi-omics data. We show that microbial species maintain stable population sizes within and across humans and that commonly used 'omics' survey methods are more reliable when using averages over multiple days of sampling. Variation of gut metabolites within people over time is associated with amino acid levels, and differences across people are associated with differences in bile acids. Finally, we show that genomic diversification can be used to infer eco-evolutionary dynamics and in vivo selection pressures for strains within individuals. The BIO-ML is a unique resource designed to enable hypothesis-driven microbiome research.


Assuntos
Bactérias/genética , Microbioma Gastrointestinal/genética , Filogenia , Seleção Genética/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Ácidos e Sais Biliares/genética , Ácidos e Sais Biliares/metabolismo , Bancos de Espécimes Biológicos , Fezes/microbiologia , Variação Genética/genética , Genoma Bacteriano/genética , Humanos , Metaboloma/genética
14.
Nat Commun ; 10(1): 4064, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492854

RESUMO

Population-based biobanks with genomic and dense phenotype data provide opportunities for generating effective therapeutic hypotheses and understanding the genomic role in disease predisposition. To characterize latent components of genetic associations, we apply truncated singular value decomposition (DeGAs) to matrices of summary statistics derived from genome-wide association analyses across 2,138 phenotypes measured in 337,199 White British individuals in the UK Biobank study. We systematically identify key components of genetic associations and the contributions of variants, genes, and phenotypes to each component. As an illustration of the utility of the approach to inform downstream experiments, we report putative loss of function variants, rs114285050 (GPR151) and rs150090666 (PDE3B), that substantially contribute to obesity-related traits and experimentally demonstrate the role of these genes in adipocyte biology. Our approach to dissect components of genetic associations across the human phenome will accelerate biomedical hypothesis generation by providing insights on previously unexplored latent structures.


Assuntos
Adipócitos/metabolismo , Bancos de Espécimes Biológicos , Estudos de Associação Genética/métodos , Estudo de Associação Genômica Ampla/métodos , Células 3T3-L1 , Adipócitos/citologia , Animais , Células Cultivadas , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/genética , Predisposição Genética para Doença/genética , Humanos , Camundongos , Obesidade/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Reino Unido
15.
Rev. argent. salud publica ; 10(40): 51-54, 30 de septiembre 2019.
Artigo em Espanhol | LILACS, BINACIS, ARGMSAL | ID: biblio-1024949

RESUMO

Los biobancos que almacenan muestras biológicas humanas y datos asociados de los donantes se han constituido en una herramienta esencial para la investigación biomédica. Su valor radica en el intercambio de las grandes cantidades de muestras y datos que almacenan para la realización de múltiples investigaciones futuras. Este nuevo escenario presenta desafíos éticos, legales y sociales relacionados con la protección de los derechos e intereses de los donantes y de la comunidad a la que pertenecen. En respuesta a estos desafíos y con el fin de promover en Argentina la existencia de biobancos con muestras de alta calidad para la realización de investigaciones con valor científico y social, que respeten en todo momento los derechos e intereses de los donantes y de la comunidad, la Secretaría de Gobierno de Salud ha elaborado una Guía de pautas éticas y legales para los biobancos con fines de investigación. Este artículo describe y analiza los puntos clave de la Guía


Assuntos
Bancos de Espécimes Biológicos , Confidencialidade , Ética em Pesquisa
18.
PLoS Genet ; 15(8): e1008277, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31369549

RESUMO

Obesity is a worldwide health problem that is closely linked to many metabolic disorders. Regular physical exercise has been found to attenuate the genetic predisposition to obesity. However, it remains unknown what kinds of exercise can modify the genetic risk of obesity. This study included 18,424 unrelated Han Chinese adults aged 30-70 years who participated in the Taiwan Biobank (TWB). A total of 5 obesity measures were investigated here, including body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Because there have been no large genome-wide association studies on obesity for Han Chinese, we used the TWB internal weights to construct genetic risk scores (GRSs) for each obesity measure, and then test the significance of GRS-by-exercise interactions. The significance level throughout this work was set at 0.05/550 = 9.1x10-5 because a total of 550 tests were performed. Performing regular exercise was found to attenuate the genetic effects on 4 obesity measures, including BMI, BFP, WC, and HC. Among the 18 kinds of self-reported regular exercise, 6 mitigated the genetic effects on at least one obesity measure. Regular jogging blunted the genetic effects on BMI, BFP, and HC. Mountain climbing, walking, exercise walking, international standard dancing, and a longer practice of yoga also attenuated the genetic effects on BMI. Exercises such as cycling, stretching exercise, swimming, dance dance revolution, and qigong were not found to modify the genetic effects on any obesity measure. Across all 5 obesity measures, regular jogging consistently presented the most significant interactions with GRSs. Our findings show that the genetic effects on obesity measures can be decreased to various extents by performing different kinds of exercise. The benefits of regular physical exercise are more impactful in subjects who are more predisposed to obesity.


Assuntos
Exercício , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Obesidade/prevenção & controle , Adulto , Bancos de Espécimes Biológicos/estatística & dados numéricos , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Autorrelato/estatística & dados numéricos , Taiwan , Circunferência da Cintura/genética , Relação Cintura-Quadril
19.
BMC Cancer ; 19(1): 765, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382921

RESUMO

BACKGROUND: Worldwide, over 500,000 people are diagnosed with head and neck cancer each year, a disease with major impact on life expectancy and quality of life. The purpose of the Netherlands Quality of life and Biomedical Cohort study (NET-QUBIC) is to advance interdisciplinary research that aims to optimize diagnosis, treatment, and supportive care for head and neck cancer patients and their informal caregivers. METHODS: Using an extensive assessment protocol (electronic clinical record form, patient reported outcome measures and fieldwork (interviews and physical tests)), clinical data and data on quality of life, demographic and personal factors, psychosocial (depression, anxiety, fatigue, pain, sleep, mental adjustment to cancer, posttraumatic stress), physical (speech, swallowing, oral function, malnutrition, physical fitness, neurocognitive function, sexual function), lifestyle (physical activity, nutrition, smoking, alcohol, drugs), and social factors (social function, social support, work, health care use, and costs) are collected and stored in the data warehouse. A longitudinal biobank is built with tumor tissue, blood and blood components, saliva samples, and oral rinses. An infrastructure for fieldwork and laboratory protocols is established at all participating centers. All patients fill out patient reported outcome measures before treatment and at 3, 6, 12, 24, 36, 48, and 60 months follow-up. The interviews, physical tests and biological sample collection are at baseline and 6, 12, and 24 months follow-up. The protocol for caregivers includes blood sampling and oral rinses at baseline and a tailored list of questionnaires, administered at the same time points as the patients. In total, 739 HNC patients and 262 informal caregivers have been included in 5 out of the 8 HNC centers in the Netherlands. DISCUSSION: By granting access to researchers to the NET-QUBIC data warehouse and biobank, we enable new research lines in clinical (e.g. treatment optimization in elderly patients), biological (e.g. liquid biopsy analysis for relapse detection), health related quality of life (e.g. the impact of toxicity on quality of life), and interrelated research (e.g. health related quality of life in relation to biomarkers and survival).


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Pesquisa Interdisciplinar/métodos , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bancos de Espécimes Biológicos , Cuidadores , Data Warehousing , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
20.
N Engl J Med ; 381(7): 668-676, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412182

RESUMO

Knowledge gained from observational cohort studies has dramatically advanced the prevention and treatment of diseases. Many of these cohorts, however, are small, lack diversity, or do not provide comprehensive phenotype data. The All of Us Research Program plans to enroll a diverse group of at least 1 million persons in the United States in order to accelerate biomedical research and improve health. The program aims to make the research results accessible to participants, and it is developing new approaches to generate, access, and make data broadly available to approved researchers. All of Us opened for enrollment in May 2018 and currently enrolls participants 18 years of age or older from a network of more than 340 recruitment sites. Elements of the program protocol include health questionnaires, electronic health records (EHRs), physical measurements, the use of digital health technology, and the collection and analysis of biospecimens. As of July 2019, more than 175,000 participants had contributed biospecimens. More than 80% of these participants are from groups that have been historically underrepresented in biomedical research. EHR data on more than 112,000 participants from 34 sites have been collected. The All of Us data repository should permit researchers to take into account individual differences in lifestyle, socioeconomic factors, environment, and biologic characteristics in order to advance precision diagnosis, prevention, and treatment.


Assuntos
Bancos de Espécimes Biológicos , Pesquisa Biomédica , Estudos de Coortes , Conjuntos de Dados como Assunto , Registros Eletrônicos de Saúde , Inquéritos Epidemiológicos , Humanos , Estudos Observacionais como Assunto , Medicina de Precisão , Projetos de Pesquisa , Estados Unidos
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