Risk factors

  • Article
    | Open Access

    The electrocardiogram (ECG) is the most commonly used exam for the screening and evaluation of cardiovascular diseases. Here, the authors propose that the age predicted by artificial intelligence from the raw ECG tracing can be a measure of cardiovascular health and provide prognostic information.

    • Emilly M. Lima
    • , Antônio H. Ribeiro
    •  & Antonio Luiz P. Ribeiro
  • Article
    | Open Access

    Maternal smoking during pregnancy contributes to poor birth outcomes. Here the authors perform a meta-analysis of the associations between maternal smoking during pregnancy and placental DNA methylation and identify links between these and poor birth outcomes, which may better inform the mechanisms through which smoking impacts placental function and fetal growth.

    • Todd M. Everson
    • , Marta Vives-Usano
    •  & Mariona Bustamante
  • Article
    | Open Access

    Detailed information on SARS-CoV-2 infection rates in Latin America by occupation, socioeconomic group and geographic area are rarely available. Here, the authors provide these estimates for in Bogota, Colombia using data from a sentinel surveillance scheme, and find that over half the population had been infected by March 2021.

    • Rachid Laajaj
    • , Camilo De Los Rios
    •  & Duncan Webb
  • Article
    | Open Access

    Diet and food intake have been associated with a risk of developing different types of cancer but individual nutritional epidemiology studies are prone to inherent bias. Here, the authors perform an umbrella review of meta-analyses of observational studies and show the level of evidence for associating food and nutrients to cancer risk.

    • Nikos Papadimitriou
    • , Georgios Markozannes
    •  & Konstantinos K. Tsilidis
  • Article
    | Open Access

    Sex and gender have been associated with differences in SARS-CoV-2 incidence and clinical outcomes and therefore warrant consideration in study designs. Here, the authors assess registered and published clinical COVID-19 studies and find that sex-disaggregated analyses are infrequently presented or planned.

    • Emer Brady
    • , Mathias Wullum Nielsen
    •  & Sabine Oertelt-Prigione
  • Article
    | Open Access

    COVID-19-related mortality in England shows geographical variation but the reasons for this are not well understood. This study estimated excess mortality in the first wave of the pandemic and found associations with higher density of care homes, overcrowding, and economic deprivation, but not with population density or air pollution.

    • Bethan Davies
    • , Brandon L. Parkes
    •  & Paul Elliott
  • Article
    | Open Access

    Mobility restrictions implemented to reduce the spread of COVID-19 have significantly impacted walking behavior. In this study, the authors integrated mobility data from mobile devices and area-level data to study the walking patterns of 1.62 million anonymous users in 10 US metropolitan areas.

    • Ruth F. Hunter
    • , Leandro Garcia
    •  & Esteban Moro
  • Article
    | Open Access

    Yellow fever virus (YFV) is an arbovirus affecting humans and non-human primates (NHPs) with seasonal transmission. Here Hamlet et al. model the monthly occurrence of YF in humans and NHPs across Brazil and show that seasonality of agriculture is an important predictor of seasonal YF transmission.

    • Arran Hamlet
    • , Daniel Garkauskas Ramos
    •  & Neil M. Ferguson
  • Article
    | Open Access

    The role of meteorological factors in SARS-COV-2 transmission is not well understood. Here, the authors use county-level data from the United States to the end of 2020 and find evidence of a moderate association between increased transmissibility and cold, dry weather and low ultraviolet radiation.

    • Yiqun Ma
    • , Sen Pei
    •  & Kai Chen
  • Article
    | Open Access

    Endocrinopathies, such as thyroid autoimmunity, are common among patients treated with immune checkpoint inhibitors. Here, by using a polygenic risk score (PRS) derived from a hypothyroidism GWAS, the authors show that cancer patients with high PRS are at increased risk of atezolizumab (anti-PD-L1)-induced thyroid dysfunction, a condition associated with systemic response to PD-1 checkpoint blockade and longer overall survival.

    • Zia Khan
    • , Christian Hammer
    •  & G. Scott Chandler
  • Article
    | Open Access

    Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

    • Itziar de Rojas
    • , Sonia Moreno-Grau
    •  & Agustín Ruiz
  • Article
    | Open Access

    Sleep dysregulation has been linked to dementia, but it is unknown whether sleep duration earlier in life is associated with dementia risk. Here, the authors show higher dementia risk associated with short sleep duration (six hours or less) in a longitudinal study of middle and older age adults.

    • Séverine Sabia
    • , Aurore Fayosse
    •  & Archana Singh-Manoux
  • Article
    | Open Access

    Digital contact tracing is increasingly considered as one of the tools to control infectious disease outbreaks, in particular the COVID-19 epidemic. Here, the authors present a modeling framework informed by empirical high-resolution contact data to analyze the impact of digital contact tracing apps.

    • G. Cencetti
    • , G. Santin
    •  & B. Lepri
  • Article
    | Open Access

    Tropical cyclones can cause severe damage and can thus have devastating impacts on societies. Here, the authors use Medicare data to show that tropical cyclone exposure in the United States is associated with increased hospitalization rates for older adults from many different acute causes.

    • Robbie M. Parks
    • , G. Brooke Anderson
    •  & Marianthi-Anna Kioumourtzoglou
  • Article
    | Open Access

    Here, the authors determine seroprevalence of antibodies to SARS-CoV-2 in healthy blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang in China between January and April 2020. The age- and sex-standardized SARS-CoV-2 seroprevalence among 18–60 year-old adults is, with 2.66%, the highest in Wuhan.

    • Le Chang
    • , Wangheng Hou
    •  & Lunan Wang
  • Article
    | Open Access

    Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.

    • Alan Bénard
    • , Anne Jacobsen
    •  & Georg F. Weber
  • Article
    | Open Access

    Identifying COVID-19 patients with the highest mortality risk early is critical to enable effective intervention and optimal prioritisation of care. Here, the authors present a clinical risk scoring system trained on a large data set of patients from 69 healthcare institutions in multiple countries.

    • Patrick Schwab
    • , Arash Mehrjou
    •  & Stefan Bauer
  • Article
    | Open Access

    Global warming is expected to increase mortality due to heat stress in many regions. Here, the authors asses how mortality due to high temperatures changes in China changes for different demographic groups and show that heat-related excess mortality is increasing under climate change, a process that is strongly amplified by population ageing.

    • Jun Yang
    • , Maigeng Zhou
    •  & Qiyong Liu
  • Article
    | Open Access

    REACT-2 is a large-scale community study of SARS-CoV-2 seroprevalence in England. Here, the authors estimate that 6% of adults in England had been infected by mid-July 2020, with health and long-term care workers and those of Black or South Asian ethnicity disproportionately affected.

    • Helen Ward
    • , Christina Atchison
    •  & Paul Elliott
  • Article
    | Open Access

    Skull base chordomas are treated with surgery and chemotherapy but often recur due to incomplete resection, understanding the molecular underpinnings of the tumours may provide additional therapeutic strategies. Here, the authors carry out whole genome sequencing of 80 skull base chordoma tumours and identify the SWI/SNF component—PBRM1—as a frequently mutated gene.

    • Jiwei Bai
    • , Jianxin Shi
    •  & Xiaohong R. Yang
  • Article
    | Open Access

    Establishing the natural history of COVID-19 requires longitudinal data from population-based cohorts. Here, the authors use linked primary care, testing, and hospital data to describe the disease in ~100,000 individuals with a COVID-19 diagnosis among a population of ~5.5 million in Catalonia, Spain.

    • Edward Burn
    • , Cristian Tebé
    •  & Talita Duarte-Salles
  • Article
    | Open Access

    Coronary artery calcium is an accurate predictor of cardiovascular events but this information is not routinely quantified. Here the authors show a robust and time-efficient deep learning system to automatically quantify coronary calcium on CT scans and predict cardiovascular events in a large, multicentre study.

    • Roman Zeleznik
    • , Borek Foldyna
    •  & Hugo J. W. L. Aerts
  • Article
    | Open Access

    The SARS-COV-2 pandemic has put pressure on intensive care units, so that predicting severe deterioration early is a priority. Here, the authors develop a multimodal severity score including clinical and imaging features that has significantly improved prognostic performance in two validation datasets compared to previous scores.

    • Nathalie Lassau
    • , Samy Ammari
    •  & Michael G. B. Blum
  • Article
    | Open Access

    The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity associated with prominent lipid accumulation in humans. Here, the authors report that the lysosomal copper transporter SLC46A3 is induced by TCDD and underlies the hepatic lipid accumulation in mice, potentially via effects on mitochondrial function.

    • Jung-Hwan Kim
    • , Tsutomu Matsubara
    •  & Frank J. Gonzalez
  • Article
    | Open Access

    Anecdotal reports suggest potential severity and outcome differences between sexes following infection by SARS-CoV-2. Here, the authors perform meta-analyses of more than 3 million cases collected from global public data to demonstrate that male patients with COVID-19 are 3 times more likely to require intensive care, and have ~40% higher death rate.

    • Hannah Peckham
    • , Nina M. de Gruijter
    •  & Claire T. Deakin
  • Article
    | Open Access

    Despite its importance for the targeting of interventions, little is known about the degree to which cardiovascular risk factors cluster within different socio-geographic levels in South Asia. Here the authors report on a cross-sectional study identifying wide variations in the clustering between risk factors and socio-geographic levels in India.

    • Anne C. Bischops
    • , Jan-Walter De Neve
    •  & Pascal Geldsetzer
  • Article
    | Open Access

    Recent evidence has suggested that blood type may be associated with severe COVID-19. Here, the authors use data from ~14,000 individuals tested for SARS-CoV-2 at a New York City hospital, and find that certain ABO and Rh blood types are associated with infection, intubation, and death.

    • Michael Zietz
    • , Jason Zucker
    •  & Nicholas P. Tatonetti
  • Article
    | Open Access

    Many published studies of the current SARS-CoV-2 pandemic have analysed data from non-representative samples from populations. Here, using UK BioBank samples, Gibran Hemani and colleagues discuss the potential for such studies to suffer from collider bias, and provide suggestions for optimising study design to account for this.

    • Gareth J. Griffith
    • , Tim T. Morris
    •  & Gibran Hemani
  • Article
    | Open Access

    Diverse toxicological mechanisms may mediate the impact of environmental toxicants on pregnancy outcomes. In this study the authors introduce an analytical framework for multivariate mediation analysis to identify mediation pathways in the relationship between environmental toxicants and gestational age at delivery.

    • Max T. Aung
    • , Yanyi Song
    •  & Bhramar Mukherjee
  • Article
    | Open Access

    Hormonal contraception may alter women’s susceptibility to HIV. Here, the authors report the results of a randomized clinical trial substudy assessing the effects of injectable Net-En, oral contraceptives (COC) and Nuvaring on vaginal microbiota and cytokines, associating COC with lower microbial diversity and Nuvaring with increased inflammation.

    • Christina Balle
    • , Iyaloo N. Konstantinus
    •  & Heather B. Jaspan
  • Article
    | Open Access

    Observationally, lower birthweight is a risk factor for cardiometabolic disease. Using Mendelian Randomization, the authors investigate whether maternal genetic factors that lower offspring birthweight also increase offspring cardiometabolic risk and show that the observational correlation is unlikely to be due to the intrauterine environment.

    • Gunn-Helen Moen
    • , Ben Brumpton
    •  & David M. Evans
  • Article
    | Open Access

    Methods to stratify patients according to mortality risk are essential to allocate limited heath resources during the COVID-19 crisis. Here, using machine learning methods, the authors present a mortality risk prediction model for COVID-19 that uses patients’ clinical data on admission to stratify patients by mortality risk.

    • Yue Gao
    • , Guang-Yao Cai
    •  & Qing-Lei Gao
  • Article
    | Open Access

    Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with COVID-19 and compare them with those admitted for influenza in previous years.

    • Edward Burn
    • , Seng Chan You
    •  & Patrick Ryan
  • Article
    | Open Access

    Early identification of COVID-19 patients at risk of progression may facilitate more individually aligned treatment plans. Here the authors develop an online nomogram incorporating CT severity score and clinical characteristics for early predicting the disease progression risk among COVID-19 pneumonia patients.

    • Zhichao Feng
    • , Qizhi Yu
    •  & Wei Wang
  • Article
    | Open Access

    Smoking-associated DNA methylation changes in whole blood have been reported by many EWAS. Here, the authors use a cell-type deconvolution algorithm to identify cell-type specific DNA methylation signals in seven EWAS, identifying lineage-specific smoking-associated DNA methylation changes.

    • Chenglong You
    • , Sijie Wu
    •  & Andrew E. Teschendorff
  • Article
    | Open Access

    The sudden deterioration of patients with novel coronavirus disease 2019 (COVID-19) into critical illness is of major concern and early assessment would be vital. Here, the authors show that a deep learning-based survival model can predict the risk of COVID-19 patients developing critical illness based on clinical characteristics at admission.

    • Wenhua Liang
    • , Jianhua Yao
    •  & Jianxing He
  • Article
    | Open Access

    Family-based study designs have been applied to resolve confounding by population stratification, dynastic effects and assortative mating in genetic association analyses. Here, Brumpton et al. describe theory and simulations for overcoming such biases in Mendelian randomization through within-family studies.

    • Ben Brumpton
    • , Eleanor Sanderson
    •  & Neil M. Davies
  • Article
    | Open Access

    Vitamin D is a precursor of the steroid hormone 1,25-dihydroxyvitamin D3, and its deficiency is associated with many adverse health outcomes. Here, Revez et al. perform a genome-wide association study for circulating 25-hydroxyvitamin D in 417,580 individuals and test for potential causal relationships with other traits using Mendelian randomization.

    • Joana A. Revez
    • , Tian Lin
    •  & John J. McGrath
  • Article
    | Open Access

    Gut microbiome has been linked to neurogenerative diseases. Here, the authors present a metagenome-wide association study of schizophrenia (SZ) in human cohorts and identify SZ-associated specific gut-brain functional modules and pathways including SCFAs and neurotransmitters.

    • Feng Zhu
    • , Yanmei Ju
    •  & Xiancang Ma