• 【英国生物银行中风险因素关联与具有常规反应率的代表性,基于一般人群的研究的比较: 前瞻性队列研究和个体参与者荟萃分析。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2020-02-12
    来源期刊:BMJ
    DOI:10.1136/bmj.m131 复制DOI
    作者列表:Batty GD,Gale CR,Kivimäki M,Deary IJ,Bell S
    BACKGROUND & AIMS: OBJECTIVE:To compare established associations between risk factors and mortality in UK Biobank, a study with an exceptionally low rate of response to its baseline survey, against those from representative studies that have conventional response rates. DESIGN:Prospective cohort study alongside individual participant meta-analysis of other cohort studies. SETTING:United Kingdom. PARTICIPANTS:Analytical sample of 499 701 people (response rate 5.5%) in analyses in UK Biobank; pooled data from the Health Surveys for England (HSE) and the Scottish Health Surveys (SHS), including 18 studies and 89 895 people (mean response rate 68%). Both study populations were linked to the same nationwide mortality registries, and the baseline age range was aligned at 40-69 years. MAIN OUTCOME MEASURE:Death from cardiovascular disease, selected malignancies, and suicide. To quantify the difference between hazard ratios in the two studies, a ratio of the hazard ratios was used with HSE-SHS as the referent. RESULTS:Risk factor levels and mortality rates were typically more favourable in UK Biobank participants relative to the HSE-SHS consortium. For the associations between risk factors and mortality endpoints, however, close agreement was seen between studies. Based on 14 288 deaths during an average of 7.0 years of follow-up in UK Biobank and 7861 deaths over 10 years of mortality surveillance in HSE-SHS, for cardiovascular disease mortality, for instance, the age and sex adjusted hazard ratio for ever having smoked cigarettes (versus never) was 2.04 (95% confidence interval 1.87 to 2.24) in UK Biobank and 1.99 (1.78 to 2.23) in HSE-SHS, yielding a ratio of hazard ratios close to unity (1.02, 0.88 to 1.19). The overall pattern of agreement between studies was essentially unchanged when results were compared separately by sex and when baseline years and censoring dates were aligned. CONCLUSION:Despite a very low response rate, risk factor associations in the UK Biobank seem to be generalisable.
    背景与目标:
  • 【英国生物库中镶嵌染色体Y丢失的预测因素及其与死亡率的关联。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-018-30759-1 复制DOI
    作者列表:Loftfield E,Zhou W,Graubard BI,Yeager M,Chanock SJ,Freedman ND,Machiela MJ
    BACKGROUND & AIMS: :Mosaic loss of the Y chromosome (mLOY) is the most commonly reported large structural somatic event. Previous studies have indicated age and cigarette smoking increase the risk of mLOY, but the relationship of other exposures with mLOY and mLOY with disease has not been adequately investigated. We characterized mLOY in a large cohort of 223,338 men from the UK Biobank by scanning for deviations in genotyping array median log2 intensity ratios (mLRR) of the Y chromosome using a standard algorithm. A total of 3,789 (1.7%) men showed evidence for mLOY (mLRR < -0.15). In multivariable-adjusted logistic regression models, we found that mLOY increases exponentially with age (overall P-value < 4.9 × 10-324; p-value for the quadratic term = 2.1 × 10-7), and observed a strong association with current smoking (P-value = 7.8 × 10-184). We observed less mLOY in men of African ancestry (0.4%) compared to men of European ancestry (1.8%, P-value = 0.003). Although mLOY was not associated with prevalent cancer (P-value = 0.61), associations were observed for diabetes (P-value = 0.003) and cardiovascular disease (P-value = 0.01). Using Cox proportional hazards regression models, mLOY was associated with all-cause mortality among men with a high proportion of cells affected (mLRR < -0.40; HR = 1.35, 95% CI = 1.08-1.70, P-value = 0.009). In conclusion, mLOY was associated with several health-related factors as well as with all-cause mortality. Further functional studies are warranted to understand how and in what way mLOY could influence adult male health.
    背景与目标: : Y染色体的镶嵌丢失 (mLOY) 是最常报道的大型结构体细胞事件。先前的研究表明,年龄和吸烟会增加mLOY的风险,但是尚未充分研究其他与mLOY和mLOY的接触与疾病的关系。我们通过使用标准算法扫描Y染色体的基因分型阵列中值log2强度比 (mLRR) 的偏差,在来自英国生物库的223,338名男性的大型队列中表征了mLOY。共有3,789 (1.7%) 名男性显示出mLOY证据 (mlrr  < -0.15)。在多变量调整logistic回归模型中,我们发现mLOY随年龄呈指数增长 (总体p值  <  4.9  ×   10-324; 二次项的p值   =   2.1  ×   10-7),并观察到与当前吸烟有很强的关联 (p值   =   7.8  ×   10-184)。与欧洲血统的男性相比,我们观察到非洲血统的男性 (0.4%) 的mLOY较少 (1.8%,p值   =   0.003)。尽管mLOY与流行的癌症无关 (p值   =   0.61),但观察到糖尿病 (p值   =   0.003) 和心血管疾病 (p值   =   0.01) 的相关性。使用Cox比例风险回归模型,mLOY与受影响细胞比例高的男性的全因死亡率相关 (mlrr  < -0.40; Hr   =   1.35,95% ci   =   1.08-1.70,p值   =   0.009)。总之,mLOY与多种健康相关因素以及全因死亡率相关。有必要进行进一步的功能研究,以了解mLOY如何以及以何种方式影响成年男性健康。
  • 【更正: 通过一项多中心纵向前瞻性队列研究推进头颈部癌症的跨学科研究: 荷兰生活质量和生物医学队列 (NET-QUBIC) 数据仓库和生物库。】 复制标题 收藏 收藏
    DOI:10.1186/s12885-019-6223-y 复制DOI
    作者列表:Verdonck-de Leeuw IM,Jansen F,Brakenhoff RH,Langendijk JA,Takes R,Terhaard CHJ,Baatenburg de Jong RJ,Smit JH,Leemans CR
    BACKGROUND & AIMS: :Following publication of the original article [1], the authors reported the name of R.J. Baatenburg de Jong was incorrectly tagged in the HTML version of the article.
    背景与目标: : 在原始文章 [1] 发布后,作者报告了R.J. Baatenburg de Jong在文章的HTML版本中被错误标记。
  • 【默认模式节点内的子专业化特征在于10,000英国生物库参与者。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.1804876115 复制DOI
    作者列表:Kernbach JM,Yeo BTT,Smallwood J,Margulies DS,Thiebaut de Schotten M,Walter H,Sabuncu MR,Holmes AJ,Gramfort A,Varoquaux G,Thirion B,Bzdok D
    BACKGROUND & AIMS: :The human default mode network (DMN) is implicated in several unique mental capacities. In this study, we tested whether brain-wide interregional communication in the DMN can be derived from population variability in intrinsic activity fluctuations, gray-matter morphology, and fiber tract anatomy. In a sample of 10,000 UK Biobank participants, pattern-learning algorithms revealed functional coupling states in the DMN that are linked to connectivity profiles between other macroscopical brain networks. In addition, DMN gray matter volume was covaried with white matter microstructure of the fornix. Collectively, functional and structural patterns unmasked a possible division of labor within major DMN nodes: Subregions most critical for cortical network interplay were adjacent to subregions most predictive of fornix fibers from the hippocampus that processes memories and places.
    背景与目标: : 人类默认模式网络 (DMN) 与几种独特的心理能力有关。在这项研究中,我们测试了DMN中大脑范围的区域间交流是否可以从固有活动波动,灰质形态和纤维束解剖结构的群体变异性中得出。在10,000个英国生物库参与者的样本中,模式学习算法揭示了DMN中的功能耦合状态,这些状态与其他宏观大脑网络之间的连通性曲线相关联。此外,DMN灰质体积与fornix的白质微观结构共同变化。总的来说,功能和结构模式掩盖了主要DMN节点内可能的分工: 对于皮质网络相互作用最关键的子区域与处理记忆和位置的海马区的最具预测能力的区域相邻。
  • 【前瞻性多发性硬化生物库样本中的爱泼斯坦-巴尔病毒抗体和维生素d。】 复制标题 收藏 收藏
    DOI:10.1177/1352458513483888 复制DOI
    作者列表:Salzer J,Nyström M,Hallmans G,Stenlund H,Wadell G,Sundström P
    BACKGROUND & AIMS: BACKGROUND:The antibody reactivity against Epstein-Barr nuclear antigen-1 (EBNA-1), and 25-hydroxyvitamin D (25(OH)D) status have been associated with multiple sclerosis (MS) risk. Interaction between these two factors has been proposed. OBJECTIVES:The objective of this paper is to examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk of MS, and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples. METHODS:Antibody reactivity and 25(OH)D levels were measured using ELISAs in n = 192 MS cases and n = 384 matched controls. The risk of MS was analysed using matched logistic regression. Interaction on the additive scale was assessed. RESULTS:The risk of MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1(402-502), and domain EBNA-1(385-420); p trends < 0.001. In young individuals (below median age at sampling, < 26.4 years), these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains. No statistical interaction was found. CONCLUSIONS:We confirm that increased antibody reactivity against EBNA-1 is a risk factor of MS. 25(OH)D status might influence the immune response towards Epstein-Barr virus in young subjects, and thereby modulate MS risk.
    背景与目标:
  • 【量化客观测量的体力活动对英国生物库死亡率的预测性能。】 复制标题 收藏 收藏
    DOI:10.1093/gerona/glaa250 复制DOI
    作者列表:Leroux A,Xu S,Kundu P,Muschelli J,Smirnova E,Chatterjee N,Crainiceanu C
    BACKGROUND & AIMS: BACKGROUND:Objective measures of physical activity (PA) derived from wrist-worn accelerometers are compared with traditional risk factors in terms of mortality prediction performance in the UK Biobank. METHODS:A subset of participants in the UK Biobank study wore a tri-axial wrist-worn accelerometer in a free-living environment for up to 7 days. A total of 82,304 individuals over the age of 50 (439,707 person-years of follow-up, 1,959 deaths) had both accelerometry data that met specified quality criteria and complete data on a set of traditional mortality risk factors. Predictive performance was assessed using cross-validated Concordance (C) for Cox regression models. Forward selection was used to obtain a set of best predictors of mortality. RESULTS:In univariate Cox regression, age was the best predictor of all-cause mortality (C=0.681) followed by twelve PA predictors, led by minutes of moderate to vigorous PA (C=0.661) and total acceleration (C=0.661). Overall, 16 of the top 20 predictors were objective PA measures (C from 0.578 to 0.661). Using a threshold of 0.001 improvement in Concordance, the Concordance for the best model that did not include PA measures was 0.735 (9 covariates) compared with 0.748 (12 covariates) for the best model with PA variables (p-value<0.001). CONCLUSIONS:Objective measures of PA derived from accelerometry outperform traditional predictors of all-cause mortality in the UK Biobank except age and substantially improve the prediction performance of mortality models based on traditional risk factors. Results confirm and complement previous findings in the National Health and Nutrition Examination Survey (NHANES).
    背景与目标:
  • 【通过次最大运动测试对全因死亡率评估的心肺健康的预后相关性: 英国生物库前瞻性研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.mayocp.2019.12.030 复制DOI
    作者列表:Laukkanen JA,Kunutsor SK,Yates T,Willeit P,Kujala UM,Khan H,Zaccardi F
    BACKGROUND & AIMS: OBJECTIVE:To investigate whether the inverse associations of cardiorespiratory fitness (CRF) with all-cause and cardiovascular mortality in the general population vary among individuals who are at different levels of pretest risk. PATIENTS AND METHODS:Cardiorespiratory fitness was assessed through submaximal bicycle tests in 58,892 participants aged 40 to 69 years who completed baseline questionnaires between January 1, 2006, and December 31, 2010, in the UK Biobank Prospective Study. Participants were categorized into risk categories, which determined allocation to an individualized bicycle protocol. The groups at minimal risk (category 1), small risk (category 2), and medium risk (category 3) were tested at 50%, 35% of the predicted maximal workload, and constant level, respectively. We investigated associations of CRF with mortality across different levels of pretest risk and determined whether CRF improves risk prediction. RESULTS:During a median follow-up of 5.8 years, 936 deaths occurred. Cardiorespiratory fitness was linearly associated with mortality risk. Comparing extreme fifths of CRF, the multivariable-adjusted hazard ratios (95% CIs) for mortality were 0.63 (0.52-0.77), 0.54 (0.36-0.82), 0.81 (0.46-1.43), and 0.58 (0.48-0.69) in categories 1, 2, and 3 and overall population, respectively. The addition of CRF to a 5-year mortality risk score containing established risk factors was associated with a C-index change (0.0012; P=.49), integrated discrimination improvement (0.0005; P<.001), net reclassification improvement (+0.0361; P=.005), and improved goodness of fit (likelihood ratio test, P<.001). Differences in 5-year survival were more pronounced across levels of age, smoking status, and sex. CONCLUSION:Cardiorespiratory fitness, assessed by submaximal exercise testing, improves mortality risk prediction beyond conventional risk factors and its prognostic relevance varies across cardiovascular risk levels.
    背景与目标:
  • 【英国生物银行中女性的遗传因素、对健康生活方式行为的坚持和浸润性乳腺癌的风险。】 复制标题 收藏 收藏
    DOI:10.1093/jnci/djz241 复制DOI
    作者列表:Arthur RS,Wang T,Xue X,Kamensky V,Rohan TE
    BACKGROUND & AIMS: BACKGROUND:Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal. METHODS:Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146 326 women from the UK Biobank. We generated an HLI score based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry, and a polygenic risk score (PRS) using 304 breast cancer-associated genetic loci. RESULTS:Among premenopausal and postmenopausal women, a favorable lifestyle (highest tertile) was associated with 22% and 31% reductions in invasive breast cancer risk, respectively (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas a high PRS (highest tertile) was associated with more than a doubling in the risk in both groups. For premenopausal women, the greatest risk reduction in association with the HLI was seen among those with a high PRS (HRhigh vs low = 0.73, 95% CI = 0.75 to 0.95). In postmenopausal women, those with a favorable lifestyle had 30%, 29%, and 32% reductions in risk of invasive breast cancer in the low, intermediate, and high PRS groups, respectively (HRhigh vs low = 0.70, 95% CI = 0.56 to 0.88; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 0.59 to 0.78, respectively). There was an additive but not multiplicative interaction between the HLI score and PRS for postmenopausal and, to a lesser extent, premenopausal women. CONCLUSION:Our findings support the view that an overall healthy lifestyle may attenuate the impact of genetic factors on invasive breast cancer risk among women of European ancestry.
    背景与目标:
  • 【通过磁共振成像评估的饮酒,心脏形态和功能之间的性别特异性关联: 来自英国生物库人口研究的见解。】 复制标题 收藏 收藏
    DOI:10.1093/ehjci/jeaa242 复制DOI
    作者列表:Simon J,Fung K,Kolossváry M,Sanghvi MM,Aung N,Paiva JM,Lukaschuk E,Carapella V,Merkely B,Bittencourt MS,Karády J,Lee AM,Piechnik SK,Neubauer S,Maurovich-Horvat P,Petersen SE
    BACKGROUND & AIMS: AIMS:Data regarding the effects of regular alcohol consumption on cardiac anatomy and function are scarce. Therefore, we sought to determine the relationship between regular alcohol intake and cardiac structure and function as evaluated with cardiac magnetic resonance imaging. METHODS AND RESULTS:Participants of the UK Biobank who underwent cardiac magnetic resonance were enrolled in our analysis. Data regarding regular alcohol consumption were obtained from questionnaires filled in by the study participants. Exclusion criteria were poor image quality, missing, or incongruent data regarding alcohol drinking habits, prior drinking, presence of heart failure or angina, and prior myocardial infarction or stroke. Overall, 4335 participants (61.5 ± 7.5 years, 47.6% male) were analysed. We used multivariate linear regression models adjusted for age, ethnicity, body mass index, smoking, hypertension, diabetes mellitus, physical activity, cholesterol level, and Townsend deprivation index to examine the relationship between regular alcohol intake and cardiac structure and function. In men, alcohol intake was independently associated with marginally increased left ventricular end-diastolic volume [β = 0.14; 95% confidence interval (CI) = 0.05-0.24; P = 0.004], left ventricular stroke volume (β = 0.08; 95% CI = 0.03-0.14; P = 0.005), and right ventricular stroke volume (β = 0.08; 95% CI = 0.02-0.13; P = 0.006). In women, alcohol consumption was associated with increased left atrium volume (β = 0.14; 95% CI = 0.04-0.23; P = 0.006). CONCLUSION:Alcohol consumption is independently associated with a marginal increase in left and right ventricular volumes in men, but not in women, whereas alcohol intake showed an association with increased left atrium volume in women. Our results suggest that there is only minimal relationship between regular alcohol consumption and cardiac morphology and function in an asymptomatic middle-aged population.
    背景与目标:
  • 【探索电子鼻技术通过呼出挥发性化合物 (VOC) 的非侵入性呼吸筛查识别间质性肺疾病 (ILD) 的能力: 来自欧洲IPF注册中心 (eurIPFreg) 和Biobank的一项试点研究。】 复制标题 收藏 收藏
    DOI:10.3390/jcm8101698 复制DOI
    作者列表:Krauss E,Haberer J,Maurer O,Barreto G,Drakopanagiotakis F,Degen M,Seeger W,Guenther A
    BACKGROUND & AIMS: BACKGROUND:There is an increasing interest in employing electronic nose technology in the diagnosis and monitoring of lung diseases. Interstitial lung diseases (ILD) are challenging in regard to setting an accurate diagnosis in a timely manner. Thus, there is a high unmet need in non-invasive diagnostic tests. This single-center explorative study aimed to evaluate the usefulness of electronic nose (Aeonose®) in the diagnosis of ILDs. METHODS:Exhaled volatile organic compound (VOC) signatures were obtained by Aeonose® in 174 ILD patients, 23 patients with chronic obstructive pulmonary disease (COPD), and 33 healthy controls (HC). RESULTS:By dichotomous comparison of VOC's between ILD, COPD, and HC, a discriminating algorithm was established. In addition, direct analyses between the ILD subgroups, e.g., cryptogenic organizing pneumonia (COP, n = 28), idiopathic pulmonary fibrosis (IPF, n = 51), and connective tissue disease-associated ILD (CTD-ILD, n = 25) were performed. Area under the Curve (AUC) and Matthews's correlation coefficient (MCC) were used to interpret the data. In direct comparison of the different ILD subgroups to HC, the algorithms developed on the basis of the Aeonose® signatures allowed safe separation between IPF vs. HC (AUC of 0.95, MCC of 0.73), COP vs. HC (AUC 0.89, MCC 0.67), and CTD-ILD vs. HC (AUC 0.90, MCC 0.69). Additionally, to a case-control study design, the breath patterns of ILD subgroups were compared to each other. Following this approach, the sensitivity and specificity showed a relevant drop, which results in a poorer performance of the algorithm to separate the different ILD subgroups (IPF vs. COP with MCC 0.49, IPF vs. CTD-ILD with MCC 0.55, and COP vs. CT-ILD with MCC 0.40). CONCLUSIONS:The Aeonose® showed some potential in separating ILD subgroups from HC. Unfortunately, when applying the algorithm to distinguish ILD subgroups from each other, the device showed low specificity. We suggest that artificial intelligence or principle compound analysis-based studies of a much broader data set of patients with ILDs may be much better suited to train these devices.
    背景与目标:
  • 【为了寻找一种基于证据的人类组织样本质量评估策略: 西班牙生物银行网络组织生物样本研究工作组的报告。】 复制标题 收藏 收藏
    DOI:10.1186/s12967-019-2124-8 复制DOI
    作者列表:Esteva-Socias M,Artiga MJ,Bahamonde O,Belar O,Bermudo R,Castro E,Escámez T,Fraga M,Jauregui-Mosquera L,Novoa I,Peiró-Chova L,Rejón JD,Ruiz-Miró M,Vieiro-Balo P,Villar-Campo V,Zazo S,Rábano A,Villena C
    BACKGROUND & AIMS: :The purpose of the present work is to underline the importance of obtaining a standardized procedure to ensure and evaluate both clinical and research usability of human tissue samples. The study, which was carried out by the Biospecimen Science Working Group of the Spanish Biobank Network, is based on a general overview of the current situation about quality assurance in human tissue biospecimens. It was conducted an exhaustive review of the analytical techniques used to evaluate the quality of human tissue samples over the past 30 years, as well as their reference values if they were published, and classified them according to the biomolecules evaluated: (i) DNA, (ii) RNA, and (iii) soluble or/and fixed proteins for immunochemistry. More than 130 publications released between 1989 and 2019 were analysed, most of them reporting results focused on the analysis of tumour and biopsy samples. A quality assessment proposal with an algorithm has been developed for both frozen tissue samples and formalin-fixed paraffin-embedded (FFPE) samples, according to the expected quality of sample based on the available pre-analytical information and the experience of the participants in the Working Group. The high heterogeneity of human tissue samples and the wide number of pre-analytic factors associated to quality of samples makes it very difficult to harmonize the quality criteria. However, the proposed method to assess human tissue sample integrity and antigenicity will not only help to evaluate whether stored human tissue samples fit for the purpose of biomarker development, but will also allow to perform further studies, such as assessing the impact of different pre-analytical factors on very well characterized samples or evaluating the readjustment of tissue sample collection, processing and storing procedures. By ensuring the quality of the samples used on research, the reproducibility of scientific results will be guaranteed.
    背景与目标: : 本工作的目的是强调获得标准化程序以确保和评估人体组织样本的临床和研究可用性的重要性。这项研究是由西班牙生物银行网络的生物样本科学工作组进行的,该研究基于对人体组织生物样本质量保证现状的总体概述。对过去30年来用于评估人体组织样品质量的分析技术以及其参考值 (如果已发表) 进行了详尽的审查,并根据评估的生物分子对其进行了分类 :( i) DNA,(ii) RNA,和 (iii) 用于免疫化学的可溶性或/和固定蛋白。对1989年发布的130多种出版物和2019进行了分析,其中大多数报告的结果集中在肿瘤和活检样本的分析上。根据可用的分析前信息和参与者的经验,根据样品的预期质量,已针对冷冻组织样品和福尔马林固定石蜡包埋 (FFPE) 样品开发了带有算法的质量评估建议在工作组中。人体组织样本的高度异质性以及与样本质量相关的大量预分析因素使得很难统一质量标准。然而,所提出的评估人体组织样品完整性和抗原性的方法不仅有助于评估储存的人体组织样品是否适合生物标志物开发的目的,而且还将允许进行进一步的研究,例如评估不同的预先分析因素对特征非常好的样品的影响,或评估组织样品收集,处理和存储程序的重新调整。通过确保用于研究的样品的质量,将保证科学结果的可重复性。
  • 【英国生物银行心肺健康与结直肠癌的关系。】 复制标题 收藏 收藏
    DOI:10.1007/s10654-019-00575-6 复制DOI
    作者列表:Hillreiner A,Baumeister SE,Sedlmeier AM,Finger JD,Schlitt HJ,Leitzmann MF
    BACKGROUND & AIMS: :Increased cardiorespiratory fitness is related to decreased risk of major chronic illnesses, including cardiovascular disease, type 2 diabetes, and cancer, but its association with colorectal cancer specifically has received very little attention. We examined the relation of cardiorespiratory fitness to colorectal cancer in 59,191 UK Biobank participants aged 39-70 years without prevalent cancer at baseline, followed from 2009 to 2014. Submaximal bicycle ergometry was conducted at study entry, and cardiorespiratory fitness was defined as physical work capacity at 75% of the maximum heart rate, standardised to body mass (PWC75%). Multivariable Cox proportional hazards regression was performed to obtain hazard ratios (HR) and corresponding 95% confidence intervals (CI). During a mean follow-up of 4.6 years, 232 participants developed colorectal cancer (151 colon cancers; 79 rectal cancers). When comparing the 75th to the 25th percentiles of PWC75%, the multivariable-adjusted HR of colorectal cancer was 0.78 (95% CI 0.62-0.97). That relation was largely driven by an inverse association with colon cancer (HR 0.74, 95% CI 0.56-0.97) and less so with rectal cancer (HR 0.88, 95% CI 0.62-1.26; p value for difference by colorectal cancer endpoint = 0.056). The inverse relation of cardiorespiratory fitness with colorectal cancer was more evident in men (HR 0.72, 95% CI 0.55-0.94) than women (HR 0.99, 95% CI 0.71-1.38), although the gender difference was not statistically significant (p value for interaction = 0.192). Increased cardiorespiratory fitness is associated with decreased risk of colorectal cancer. Potential heterogeneity by colorectal cancer anatomic subsite and gender requires further study.
    背景与目标: : 心肺功能的增强与主要慢性疾病 (包括心血管疾病,2型糖尿病和癌症) 的风险降低有关,但其与结直肠癌的相关性却很少受到关注。我们在59,191名年龄39-70岁的英国生物库参与者中,在基线时没有流行癌症,随后2009年2014年检查了心肺适应性与结直肠癌的关系。在研究开始时进行次最大自行车测功,并将心肺适应性定义为最大心率75% 时的体力劳动能力,并标准化为体重 (PWC75 %)。进行多变量Cox比例风险回归以获得风险比 (HR) 和相应的95% 置信区间 (CI)。在平均4.6年的随访中,232名参与者发展为结直肠癌 (151例结肠癌; 79例直肠癌)。当比较PWC75% 的第75至第25百分位数时,结直肠癌的多变量调整HR为0.78 (95% CI 0.62-0.97)。这种关系主要由与结肠癌的反向关联 (HR 0.74,95% CI 0.56-0.97) 驱动,而与直肠癌的反向关联较少 (HR 0.88,95% CI 0.62-1.26; 结直肠癌终点差异的p值   =   0.056)。男性 (HR 0.72,95% CI 0.55-0.94) 与女性 (HR 0.99,95% CI 0.71-1.38) 的心肺适性与结直肠癌的反比关系更为明显,但性别差异无统计学意义 (交互作用p值   =   0.192)。心肺适应性增强与结直肠癌风险降低相关。大肠癌解剖亚位点和性别的潜在异质性需要进一步研究。
  • 【健身和握力与心力衰竭的关联: 来自英国生物银行基于人群的研究的结果。】 复制标题 收藏 收藏
    DOI:10.1016/j.mayocp.2019.04.041 复制DOI
    作者列表:Sillars A,Celis-Morales CA,Ho FK,Petermann F,Welsh P,Iliodromiti S,Ferguson LD,Lyall DM,Anderson J,Mackay DF,Pellicori P,Cleland J,Pell JP,Gill JMR,Gray SR,Sattar N
    BACKGROUND & AIMS: OBJECTIVE:To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data. PATIENTS AND METHODS:Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders. RESULTS:During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1-metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72). CONCLUSION:Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal.
    背景与目标:
  • 【英国生物银行女性生殖史与慢性阻塞性肺疾病和肺功能的关系: 一项基于人群的前瞻性队列研究。】 复制标题 收藏 收藏
    DOI:10.1136/bmjopen-2019-030318 复制DOI
    作者列表:Tang R,Fraser A,Magnus MC
    BACKGROUND & AIMS: OBJECTIVES:Sex differences in respiratory physiology and predilection for developing chronic obstructive pulmonary disease (COPD) have been documented, suggesting that female sex hormones may influence pathogenesis. We investigated whether aspects of female reproductive health might play a role in risk of COPD among women. DESIGN:Population-based prospective cohort study. SETTING:UK Biobank recruited across 22 centres in the UK between 2006 to 2010. PRIMARY AND SECONDARY OUTCOMES MEASURES:We examined a range of female reproductive health indicators in relation to risk of COPD-related hospitalisation/death (n=271 271) using Cox proportional hazards regression; and lung function (n=273 441) using linear regression. RESULTS:Parity >3 was associated with greater risk of COPD-related hospitalisation/death (adjusted HR 1.45; 95% CI: 1.16 to 1.82) and lower forced expiratory volume at 1 second/forced vital capacity ratio (FEV1/FVC) (adjusted mean difference -0.06; 95% CI: -0.07 to 0.04). Any oral contraception use was associated with lower risk of COPD-related hospitalisation/death (adjusted HR 0.85; 95% CI: 0.74 to 0.97) and greater FEV1/FVC (adjusted mean difference 0.01; 95% CI: 0.003 to 0.03). Late menarche (age >15) and early menopause (age <47) were also associated with greater risk of COPD-related hospitalisation/death (but not lung function), while endometriosis was associated with greater FEV1/FVC (not COPD-related hospitalisation/death). Early menarche (age <12 years) was associated with lower FEV1/FVC (but not COPD hospitalisation/death). Associations with polycystic ovary syndrome (PCOS) or ovarian cysts, any hormone replacement therapy (HRT) use, hysterectomy-alone and both hysterectomy and bilateral oophorectomy were in opposing directions for COPD-related hospitalisation/death (greater risk) and FEV1/FVC (positive association). CONCLUSIONS:Multiple female reproductive health indicators across the life course are associated with COPD-related hospitalisation/death and lung function. Further studies are necessary to understand the opposing associations of PCOS/ovarian cysts, HRT and hysterectomy with COPD and objective measures of airway obstruction.
    背景与目标:
  • 【甲状腺状态对局部脑体积的影响: 英国生物库的诊断和遗传成像研究。】 复制标题 收藏 收藏
    DOI:10.1210/clinem/dgaa903 复制DOI
    作者列表:Chambers T,Anney R,Taylor PN,Teumer A,Peeters RP,Medici M,Caseras X,Rees DA
    BACKGROUND & AIMS: BACKGROUND:Thyroid hormone is essential for optimal human neurodevelopment and may modify the risk of attention-deficit hyperactivity disorder (ADHD). However, the brain structures involved are unknown and it is unclear if the adult brain is also susceptible to changes in thyroid status. METHODS:We used international classification of disease-10 codes, polygenic thyroid scores at different thresholds of association with thyroid traits (pT-values) and image-derived phenotypes in UK Biobank (n=18,825) to investigate the effects of a recorded diagnosis of thyroid disease and genetic risk for thyroid status on cerebellar and subcortical grey matter volume. Regional genetic pleiotropy between thyroid status and ADHD was explored using the GWAS-pairwise method. RESULTS:A recorded diagnosis of hypothyroidism (n=419) was associated with significant reductions in total cerebellar and pallidum grey matter volumes (β[95%CI] = -0.14[-0.23, -0.06], p = 0.0005 and β[95%CI] = -0.12[-0.20, -0.04], p = 0.0042, respectively), mediated in part by increases in Body Mass Index. Whilst we found no evidence for total cerebellar volume alterations with increased polygenic scores for any thyroid trait, opposing influences of increased polygenic scores for hypo- and hyperthyroidism were found in the pallidum (pT<1e-3: β[95%CI] = -0.02[-0.03,-0.01], p = 0.0003 and pT<1e-7: β[95%CI] = 0.02[0.01,0.03], p = 0.0003, respectively). Neither hypo- nor hyperthyroidism showed evidence of regional genetic pleiotropy with ADHD. CONCLUSIONS:Thyroid status affects grey matter volume in adults, particularly at the level of the cerebellum and pallidum, with potential implications for the regulation of motor, cognitive and affective function.
    背景与目标:

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