Periodic Reporting for period 2 - CHRONO (Chronotype, health and family: The role of biology, socio- and natural environment and their interaction) Período documentado: 2021-05-01 hasta 2022-10-31 Resumen del contexto y de los objetivos generales del proyecto Problem being addressed. CHRONO examines the role of biology, differences in the social and natural environment and their interaction on understanding resilience to chronotype disruption and how these in turn impact health and family domains. Health outcomes include sleep, cancer, obesity and digestive problems with family research examining partnerships (sexual behaviour, union formation, dissolution, conflict), parent-child interaction and fertility. What is it important for society? We all have a chronotype – known as an internal clock, circadian rhythm or ‘zeitgeber’ – which tells our bodies when to sleep, wake and eat and is affected by light cues. Recent changes such as increased light pollution (indoor, streets) and the widespread use of laptops and smartphones, places more individuals at risk of circadian disruption. Exposure to artificial light, particularly before bedtime, reduces sleep duration and quality. The rise of the 24-hour service economy and COVID-19 induced changes in working has likewise generated increased demands for night, shift and weekend work. In fact, 17% of employed Europeans regularly work evenings (6-10pm) and 6% night shifts (10pm-6am). Many now push their bodies against and beyond their clocks’ capabilities, with a staggering 25% reporting insomnia. Sleep deprivation is related to lower cognitive functioning, more accidents and increased interpersonal conflict, with chronotype disruption a ‘ticking time bomb of long-term health risks’. CHRONO has the potential to overturn long-held substantive findings and generate a unique new body of research. This includes for example challenging whether night shift work is causally carcinogenic or whether reported chronotype preference is simply an adaption to schedules rather than an intrinsic clock. What are the overall objectives? The project has five main objectives: (1) develop a multifactor interdisciplinary theoretical model; (2) crowdsource a new sociogenomic dataset with novel precision measures and population diversity; (3) discover and validate innovative measures of chronotype; socio- (e.g. working time regulations) and geo-linked data (e.g. light); (4) ask new substantive questions to determine how chronotype disruption influences health and family outcomes and, via Biology x Environment (BxE) interaction, whether this is moderated by the natural or socio-environment; (5) develop new statistical models and methods to cope with contentious issues, address longitudinal questions and engage in novel natural experiments to transcend description to identify endogenous factors and causal mechanisms. Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha The pandemic caused considerable disruption but also opportunities for CHRONO. Given that the pandemic changed many working patterns and locations and timing, a fundamental research topic of CHRONO, we were ideally positioned as a new team to integrate COVID transformations of society, working and living into the project. The research output of the project has exceeded our original goals during this first period, in spite of remote working and the pandemic. At the mid-term phase of this project, the team has made the following key contributions: 1. Extension of sub-field of sociogenomics. This includes the discovery of genetic variants linked to behavioural outcomes, fertility and externalising behaviour, in which the polygenic scores and research can be used as a basis for the second part of CHRONO (in Mills et al. 2021 Nature HB; Mattheison et al. forthcoming 2022). We also launched the GWAS (genome wide association study) Diversity Monitor (www.gwasdiversitymonitor.com) published in Nature Genetics (2020) to monitor the (lack of) ancestral diversity in genetic data by disease, over time and by multiple traits. We are currently extending this and it has been used widely. A more critical, sociological reflection about dismantling biological race and genetic essentialism narratives was also published in Herd, Dowd and Mills (2021). Reviews of work and theoretical and methodological reflections are in Mills & Tropf (2020) and Mills (2022), with a focus on the statistical and programming applications the book Mills et al. (2020). 2. Many COVID-19 themed publications were integrated as a new research theme in CHRONO, with considerable citations to date and policy impact. COVID disrupted this project, but also raised new research questions, a natural experiment and opportunities that could be integrated into the original objectives. Publications include the demographic composition of populations and expected COVID-19 deaths (Dowd et al. PNAS, ~900 citations), interdisciplinary combination of social network with epidemiology disease models to model interaction (Block et al. 2020, ~400 citations), several articles quantifying the burden and impact of COVID on health, life expectancy and mortality (Aburto et al. 2021 (100 citations); Aburto et al. 2022 (150 citations); gender differences in sleep disruption during COVID-19 (Ding et al. 2022); mapping inequality and hospital deserts (Verhagen et al. 2022 (55 citations); inequality and inability to follow COVID-19 non-pharmaceutical interventions and infections (Ding et la. 2021 BMJ); behavioural and demographic approaches related to vaccinations (Jennings et al 2021 (120 citations); Mills & Salisbury 2021 (90 citations); Razai et al 2021 (50 citations)) and certification (Dye & Mills 2021 (invited Science 2021 Editorial); Mills & Ruttenhauer 2022, Lancet Public Health; 55 citations).3. Building the ethics, legal, governance, scientific and technical infrastructure for the GDPR-compliant crowd-based primary data collection. This has been further extended and supported by the award of a Proof of Concept Award (DNA4Science) to allow other approved scientists to ethically use the data in the auspices of a social enterprise spin-out company launched by the PI. 4. Substantial knowledge transfer in the form of public media appearances explaining research and implications for the general public, (inter)national policy impact and participation in key advisor roles for UK government and European Commission. Several international awards and recognition of innovation were also granted to the PI from the Population Association of America (Clifford C. Clogg Award for mid-career achievement) and the Trailblazer Award from the European Association of Population Studies. 5. Several novel methodologies were used and developed in the first phase of this project. This included exposing the problem of collider bias in models that incorporate molecular genetic data and offering some solutions (Akimova et al. 2021, Nature Sci Rep), estimation bias in genome-wide association studies using a within-sibling family based design (Howe et al. 2022, Nature Genetics) and quantified the impact of the COVID-19 pandemic of health and life expectancy losses in 29 countries (Aburto et al. 2021). Another creative application was the use of synthetic cohort modelling to produce a counterfactual explanation to identify causal mechanisms of policies on health (hospitalization, infections, death) and vaccination uptake (Mills & Rüttenauer 2021, Lancet Public Health). Finally, we applied new types of simulations combining stochastic infection curve models from epidemiology with social network and statistical relational event models used in sociology (Block et al. 2020, Nature Human Behavior). 6. Interdisciplinary developments continued and were expanded as well, with application of theories, methods and data from sociology, demography, molecular genetics, biology, econometrics, statistics and epidemiology. It is notable that publications in the CHRONO project span multiple disciplines, but also are published in the highest journals in those disciplines, including sociology and demography (e.g. Annual Review Sociology, European Sociological Review, Population Studies), genetics (Nature Genetics x 2), epidemiology, medicine and public health (Nature Medicine, BMJ, Journal of Epidemiology and Community Health Science, BMC Medicine) and top general science journals (Science, PNAS, Nature Sci Reports). Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha) Our interdisciplinary work has pushed boundaries in this area of research by discovering the genetics of new types of behavioural outcomes and their interaction with the social and natural environment. We also discovered genetic overlaps between behavioural outcomes and interrogated correlation and causality in new ways that extend our understanding. In this next phase of the project, we will launch our innovative crowdsourced data collection project, which will host a wealth of data that allows us to examine our topics in new ways, using fundamentally new measures and work further on validating innovative measures and models.