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Psychological well-being, characterized by feelings, cognitions, and strategies that are associated with positive functioning (including hedonic and eudaimonic well-being), has been linked with better physical health and greater longevity. Importantly, psychological well-being can be strengthened with interventions, providing a strategy for improving population health. But are the effects of well-being interventions meaningful, durable, and scalable enough to improve health at a population-level? To assess this possibility, a cross-disciplinary group of scholars convened to review current knowledge and develop a research agenda. Here we summarize and build on the key insights from this convening, which were: (1) existing interventions should continue to be adapted to achieve a large-enough effect to result in downstream improvements in psychological functioning and health, (2) research should determine the durability of interventions needed to drive population-level and lasting changes, (3) a shift from individual-level care and treatment to a public-health model of population-level prevention is needed and will require new infrastructure that can deliver interventions at scale, (4) interventions should be accessible and effective in racially, ethnically, and geographically diverse samples. A discussion examining the key future research questions follows.

Psychological well-being, characterized by feelings, cognitions, and strategies that are associated with positive functioning (including hedonic and eudaimonic well-being), has been linked with better physical health and greater longevity. Importantly, psychological well-being can be strengthened with interventions, providing a strategy for improving population health. But are the effects of well-being interventions meaningful, durable, and scalable enough to improve health at a population-level? To assess this possibility, a cross-disciplinary group of scholars convened to review current knowledge and develop a research agenda. Here we summarize and build on the key insights from this convening, which were: (1) existing interventions should continue to be adapted to achieve a large-enough effect to result in downstream improvements in psychological functioning and health, (2) research should determine the durability of interventions needed to drive population-level and lasting changes, (3) a shift from individual-level care and treatment to a public-health model of population-level prevention is needed and will require new infrastructure that can deliver interventions at scale, (4) interventions should be accessible and effective in racially, ethnically, and geographically diverse samples. A discussion examining the key future research questions follows.

COVID-19 has infected millions of people and upended the lives of most humans on the planet. Researchers from across the psychological sciences have sought to document and investigate the impact of COVID-19 in myriad ways, causing an explosion of research that is broad in scope, varied in methods, and challenging to consolidate. Because policy and practice aimed at helping people live healthier and happier lives requires insight from robust patterns of evidence, this article provides a rapid and thorough summary of high-quality studies available through early 2021 examining the mental-health consequences of living through the COVID-19 pandemic. Our review of the evidence indicates that anxiety, depression, and distress increased in the early months of the pandemic. Meanwhile, suicide rates, life satisfaction, and loneliness remained largely stable throughout the first year of the pandemic. In response to these insights, we present seven recommendations (one urgent, two short-term, and four ongoing) to support mental health during the pandemic and beyond.

COVID-19 has infected millions of people and upended the lives of most humans on the planet. Researchers from across the psychological sciences have sought to document and investigate the impact of COVID-19 in myriad ways, causing an explosion of research that is broad in scope, varied in methods, and challenging to consolidate. Because policy and practice aimed at helping people live healthier and happier lives requires insight from robust patterns of evidence, this article provides a rapid and thorough summary of high-quality studies available through early 2021 examining the mental-health consequences of living through the COVID-19 pandemic. Our review of the evidence indicates that anxiety, depression, and distress increased in the early months of the pandemic. Meanwhile, suicide rates, life satisfaction, and loneliness remained largely stable throughout the first year of the pandemic. In response to these insights, we present seven recommendations (one urgent, two short-term, and four ongoing) to support mental health during the pandemic and beyond.

BACKGROUND: Little research has examined associations between disaster-related home loss and multiple domains of health and well-being, with extended long-term follow-up and comprehensive adjustment for pre-disaster characteristics of survivors. OBJECTIVES: We examined the longitudinal associations between disaster-induced home loss and 34 indicators of health and well-being, assessed similar to 9 y post-disaster. METHODS: We used data from a preexisting cohort study of Japanese older adults in an area directly impacted by the 2011 Japan Earthquake (n = 3,350 and n = 2,028, depending on the outcomes). The study was initiated in 2010, and disaster-related home loss status was measured in 2013 retrospectively. The 34 outcomes were assessed in 2020 and covered dimensions of physical health, mental health, health behaviors/sleep, social well-being, cognitive social capital, subjective well-being, and prosocial/altruistic behaviors. We estimated the associations between disaster-related home loss and the outcomes, using targeted maximum likelihood estimation and SuperLearner. We adjusted for pre-disaster characteristics from the wave conducted 7 months before the disaster (i.e., 2010), including prior outcome values that were available. RESULTS: After Bonferroni correction for multiple testing, we found that home loss (vs. no home loss) was associated with increased posttraumatic stress symptoms (standardized difference = 0.50; 95% CI: 0.35, 0.65), increased daily sleepiness (0.38; 95% CI: 0.21, 0.54), lower trust in the community (-0.36; 95% CI: -0.53, -0.18), lower community attachment (-0.60; 95% CI: -0.75, -0.45), and lower prosociality (-0.39; 95% CI: -0.55, -0.24). We found modest evidence for the associations with increased depressive symptoms, increased hopelessness, more chronic conditions, higher body mass index, lower perceived mutual help in the community, and decreased happiness. There was little evidence for associations with the remaining 23 outcomes. DISC, Funding Agencies|National Institutes of Health; Japan Society for the Promotion of Science [R01 AG042463]; Health Labour Sciences Research Grant from the Japanese Ministry of Health, Labour, and Welfare [KAKENHI 23243070, KAKENHI 22390400, KAKENHI 20H00557, KAKENHI 24390469]; Strategic Research Foundation Grant-Aided Project for Private Universities from the Japanese Ministry of Education, Culture, Sports, Science, and Technology [H24-Choju-Wakate-009]; Japan Agency for Medical Research and Development [S0991035]; Well-being for Planet Earth Foundation [JP17dk0110017, JP18dk0110027, JP18ls0110002, JP18le0110009, JP19dk0110034, JP19dk0110037, JP20dk0110034]; Japan Society for the Promotion of Science Research Fellowship for Young Scientists; Swedish Research Council [KAKENHI 21J01171]; Royal Swedish Academy of Letters, History, and Antiquities, Stockholm, Sweden

BACKGROUND: Little research has examined associations between disaster-related home loss and multiple domains of health and well-being, with extended long-term follow-up and comprehensive adjustment for pre-disaster characteristics of survivors. OBJECTIVES: We examined the longitudinal associations between disaster-induced home loss and 34 indicators of health and well-being, assessed similar to 9 y post-disaster. METHODS: We used data from a preexisting cohort study of Japanese older adults in an area directly impacted by the 2011 Japan Earthquake (n = 3,350 and n = 2,028, depending on the outcomes). The study was initiated in 2010, and disaster-related home loss status was measured in 2013 retrospectively. The 34 outcomes were assessed in 2020 and covered dimensions of physical health, mental health, health behaviors/sleep, social well-being, cognitive social capital, subjective well-being, and prosocial/altruistic behaviors. We estimated the associations between disaster-related home loss and the outcomes, using targeted maximum likelihood estimation and SuperLearner. We adjusted for pre-disaster characteristics from the wave conducted 7 months before the disaster (i.e., 2010), including prior outcome values that were available. RESULTS: After Bonferroni correction for multiple testing, we found that home loss (vs. no home loss) was associated with increased posttraumatic stress symptoms (standardized difference = 0.50; 95% CI: 0.35, 0.65), increased daily sleepiness (0.38; 95% CI: 0.21, 0.54), lower trust in the community (-0.36; 95% CI: -0.53, -0.18), lower community attachment (-0.60; 95% CI: -0.75, -0.45), and lower prosociality (-0.39; 95% CI: -0.55, -0.24). We found modest evidence for the associations with increased depressive symptoms, increased hopelessness, more chronic conditions, higher body mass index, lower perceived mutual help in the community, and decreased happiness. There was little evidence for associations with the remaining 23 outcomes. DISC, Funding Agencies|National Institutes of Health; Japan Society for the Promotion of Science [R01 AG042463]; Health Labour Sciences Research Grant from the Japanese Ministry of Health, Labour, and Welfare [KAKENHI 23243070, KAKENHI 22390400, KAKENHI 20H00557, KAKENHI 24390469]; Strategic Research Foundation Grant-Aided Project for Private Universities from the Japanese Ministry of Education, Culture, Sports, Science, and Technology [H24-Choju-Wakate-009]; Japan Agency for Medical Research and Development [S0991035]; Well-being for Planet Earth Foundation [JP17dk0110017, JP18dk0110027, JP18ls0110002, JP18le0110009, JP19dk0110034, JP19dk0110037, JP20dk0110034]; Japan Society for the Promotion of Science Research Fellowship for Young Scientists; Swedish Research Council [KAKENHI 21J01171]; Royal Swedish Academy of Letters, History, and Antiquities, Stockholm, Sweden

BACKGROUND: Little research has examined associations between disaster-related home loss and multiple domains of health and well-being, with extended long-term follow-up and comprehensive adjustment for pre-disaster characteristics of survivors. OBJECTIVES: We examined the longitudinal associations between disaster-induced home loss and 34 indicators of health and well-being, assessed similar to 9 y post-disaster. METHODS: We used data from a preexisting cohort study of Japanese older adults in an area directly impacted by the 2011 Japan Earthquake (n = 3,350 and n = 2,028, depending on the outcomes). The study was initiated in 2010, and disaster-related home loss status was measured in 2013 retrospectively. The 34 outcomes were assessed in 2020 and covered dimensions of physical health, mental health, health behaviors/sleep, social well-being, cognitive social capital, subjective well-being, and prosocial/altruistic behaviors. We estimated the associations between disaster-related home loss and the outcomes, using targeted maximum likelihood estimation and SuperLearner. We adjusted for pre-disaster characteristics from the wave conducted 7 months before the disaster (i.e., 2010), including prior outcome values that were available. RESULTS: After Bonferroni correction for multiple testing, we found that home loss (vs. no home loss) was associated with increased posttraumatic stress symptoms (standardized difference = 0.50; 95% CI: 0.35, 0.65), increased daily sleepiness (0.38; 95% CI: 0.21, 0.54), lower trust in the community (-0.36; 95% CI: -0.53, -0.18), lower community attachment (-0.60; 95% CI: -0.75, -0.45), and lower prosociality (-0.39; 95% CI: -0.55, -0.24). We found modest evidence for the associations with increased depressive symptoms, increased hopelessness, more chronic conditions, higher body mass index, lower perceived mutual help in the community, and decreased happiness. There was little evidence for associations with the remaining 23 outcomes. DISC, Funding Agencies|National Institutes of Health; Japan Society for the Promotion of Science [R01 AG042463]; Health Labour Sciences Research Grant from the Japanese Ministry of Health, Labour, and Welfare [KAKENHI 23243070, KAKENHI 22390400, KAKENHI 20H00557, KAKENHI 24390469]; Strategic Research Foundation Grant-Aided Project for Private Universities from the Japanese Ministry of Education, Culture, Sports, Science, and Technology [H24-Choju-Wakate-009]; Japan Agency for Medical Research and Development [S0991035]; Well-being for Planet Earth Foundation [JP17dk0110017, JP18dk0110027, JP18ls0110002, JP18le0110009, JP19dk0110034, JP19dk0110037, JP20dk0110034]; Japan Society for the Promotion of Science Research Fellowship for Young Scientists; Swedish Research Council [KAKENHI 21J01171]; Royal Swedish Academy of Letters, History, and Antiquities, Stockholm, Sweden

BACKGROUND: Little research has examined associations between disaster-related home loss and multiple domains of health and well-being, with extended long-term follow-up and comprehensive adjustment for pre-disaster characteristics of survivors. OBJECTIVES: We examined the longitudinal associations between disaster-induced home loss and 34 indicators of health and well-being, assessed similar to 9 y post-disaster. METHODS: We used data from a preexisting cohort study of Japanese older adults in an area directly impacted by the 2011 Japan Earthquake (n = 3,350 and n = 2,028, depending on the outcomes). The study was initiated in 2010, and disaster-related home loss status was measured in 2013 retrospectively. The 34 outcomes were assessed in 2020 and covered dimensions of physical health, mental health, health behaviors/sleep, social well-being, cognitive social capital, subjective well-being, and prosocial/altruistic behaviors. We estimated the associations between disaster-related home loss and the outcomes, using targeted maximum likelihood estimation and SuperLearner. We adjusted for pre-disaster characteristics from the wave conducted 7 months before the disaster (i.e., 2010), including prior outcome values that were available. RESULTS: After Bonferroni correction for multiple testing, we found that home loss (vs. no home loss) was associated with increased posttraumatic stress symptoms (standardized difference = 0.50; 95% CI: 0.35, 0.65), increased daily sleepiness (0.38; 95% CI: 0.21, 0.54), lower trust in the community (-0.36; 95% CI: -0.53, -0.18), lower community attachment (-0.60; 95% CI: -0.75, -0.45), and lower prosociality (-0.39; 95% CI: -0.55, -0.24). We found modest evidence for the associations with increased depressive symptoms, increased hopelessness, more chronic conditions, higher body mass index, lower perceived mutual help in the community, and decreased happiness. There was little evidence for associations with the remaining 23 outcomes. DISC, Funding Agencies|National Institutes of Health; Japan Society for the Promotion of Science [R01 AG042463]; Health Labour Sciences Research Grant from the Japanese Ministry of Health, Labour, and Welfare [KAKENHI 23243070, KAKENHI 22390400, KAKENHI 20H00557, KAKENHI 24390469]; Strategic Research Foundation Grant-Aided Project for Private Universities from the Japanese Ministry of Education, Culture, Sports, Science, and Technology [H24-Choju-Wakate-009]; Japan Agency for Medical Research and Development [S0991035]; Well-being for Planet Earth Foundation [JP17dk0110017, JP18dk0110027, JP18ls0110002, JP18le0110009, JP19dk0110034, JP19dk0110037, JP20dk0110034]; Japan Society for the Promotion of Science Research Fellowship for Young Scientists; Swedish Research Council [KAKENHI 21J01171]; Royal Swedish Academy of Letters, History, and Antiquities, Stockholm, Sweden

BACKGROUND: Little research has examined associations between disaster-related home loss and multiple domains of health and well-being, with extended long-term follow-up and comprehensive adjustment for pre-disaster characteristics of survivors. OBJECTIVES: We examined the longitudinal associations between disaster-induced home loss and 34 indicators of health and well-being, assessed similar to 9 y post-disaster. METHODS: We used data from a preexisting cohort study of Japanese older adults in an area directly impacted by the 2011 Japan Earthquake (n = 3,350 and n = 2,028, depending on the outcomes). The study was initiated in 2010, and disaster-related home loss status was measured in 2013 retrospectively. The 34 outcomes were assessed in 2020 and covered dimensions of physical health, mental health, health behaviors/sleep, social well-being, cognitive social capital, subjective well-being, and prosocial/altruistic behaviors. We estimated the associations between disaster-related home loss and the outcomes, using targeted maximum likelihood estimation and SuperLearner. We adjusted for pre-disaster characteristics from the wave conducted 7 months before the disaster (i.e., 2010), including prior outcome values that were available. RESULTS: After Bonferroni correction for multiple testing, we found that home loss (vs. no home loss) was associated with increased posttraumatic stress symptoms (standardized difference = 0.50; 95% CI: 0.35, 0.65), increased daily sleepiness (0.38; 95% CI: 0.21, 0.54), lower trust in the community (-0.36; 95% CI: -0.53, -0.18), lower community attachment (-0.60; 95% CI: -0.75, -0.45), and lower prosociality (-0.39; 95% CI: -0.55, -0.24). We found modest evidence for the associations with increased depressive symptoms, increased hopelessness, more chronic conditions, higher body mass index, lower perceived mutual help in the community, and decreased happiness. There was little evidence for associations with the remaining 23 outcomes. DISC, Funding Agencies|National Institutes of Health; Japan Society for the Promotion of Science [R01 AG042463]; Health Labour Sciences Research Grant from the Japanese Ministry of Health, Labour, and Welfare [KAKENHI 23243070, KAKENHI 22390400, KAKENHI 20H00557, KAKENHI 24390469]; Strategic Research Foundation Grant-Aided Project for Private Universities from the Japanese Ministry of Education, Culture, Sports, Science, and Technology [H24-Choju-Wakate-009]; Japan Agency for Medical Research and Development [S0991035]; Well-being for Planet Earth Foundation [JP17dk0110017, JP18dk0110027, JP18ls0110002, JP18le0110009, JP19dk0110034, JP19dk0110037, JP20dk0110034]; Japan Society for the Promotion of Science Research Fellowship for Young Scientists; Swedish Research Council [KAKENHI 21J01171]; Royal Swedish Academy of Letters, History, and Antiquities, Stockholm, Sweden

Happiness is an increasingly prominent topic of interest across academia. However, relatively little attention has been paid to how it is created, especially not in a multidimensional sense. By ‘created’ we do not mean its influencing factors, for which there is extensive research, but how it actually forms in the person. The work that has been done in this arena tends to focus on physiological dynamics, which are certainly part of the puzzle. But they are not the whole picture, with psychological, phenomenological, and socio cultural processes also playing their part. As a result, this paper offers a multidimensional overview of scholarship on the ‘architecture’ of happiness, providing a stimulus for further work into this important topic.

Measures of well-being have proliferated over the past decades. Very little guidance has been available as to which measures to use in what contexts. This paper provides a series of recommendations, based on the present state of knowledge and the existing measures available, of what measures might be preferred in which contexts. The recommendations came out of an interdisciplinary workshop on the measurement of well-being. The recommendations are shaped around the number of items that can be included in a survey, and also based on the differing potential contexts and purposes of data collection such as, for example, government surveys, or multi-use cohort studies, or studies specifically about psychological well-being. The recommendations are not intended to be definitive, but to stimulate discussion and refinement, and to provide guidance to those relatively new to the study of well-being.

Measures of well-being have proliferated over the past decades. Very little guidance has been available as to which measures to use in what contexts. This paper provides a series of recommendations, based on the present state of knowledge and the existing measures available, of what measures might be preferred in which contexts. The recommendations came out of an interdisciplinary workshop on the measurement of well-being. The recommendations are shaped around the number of items that can be included in a survey, and also based on the differing potential contexts and purposes of data collection such as, for example, government surveys, or multi-use cohort studies, or studies specifically about psychological well-being. The recommendations are not intended to be definitive, but to stimulate discussion and refinement, and to provide guidance to those relatively new to the study of well-being.

COVID-19 has infected millions of people and upended the lives of most humans on the planet. Researchers from across the psychological sciences have sought to document and investigate the impact of COVID-19 in myriad ways, causing an explosion of research that is broad in scope, varied in methods, and challenging to consolidate. Because policy and practice aimed at helping people live healthier and happier lives requires insight from robust patterns of evidence, this paper provides a rapid and thorough summary of high-quality studies available through early 2021 examining the mental health consequences of living through the COVID-19 pandemic. Our review of the evidence indicates that anxiety, depression, and distress increased in the early months of the pandemic. Meanwhile, suicide rates, life satisfaction, and loneliness remained largely stable throughout the first year of the pandemic. In response to these insights, we present seven recommendations (one urgent, two short-term, and four ongoing) to support mental health during the pandemic and beyond.

Importance: Mendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias from confounding and reverse causation. Objective: To develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies. Design, Setting, and Participants: The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design users, developers of previous reporting guidelines, and journal editors, participated in a workshop in May 2019 to define the scope of the Statement and draft the checklist. The draft checklist was published as a preprint in July 2019 and discussed on the preprint platform, in social media, and at the 4th Mendelian Randomization Conference. The checklist was then revised based on comments, further refined through 2020, and finalized in July 2021. Findings: The STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems. It covers both 1-sample and 2-sample MR studies that assess 1 or multiple exposures and outcomes, and addresses MR studies that follow a genome-wide association study and are reported in the same article. The checklist asks authors to justify why MR is a helpful method to address the study question and state prespecified causal hypotheses. The measurement, quality, and selection of genetic variants must be described and attempts to assess validi

Importance: Mendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias from confounding and reverse causation. Objective: To develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies. Design, Setting, and Participants: The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design users, developers of previous reporting guidelines, and journal editors, participated in a workshop in May 2019 to define the scope of the Statement and draft the checklist. The draft checklist was published as a preprint in July 2019 and discussed on the preprint platform, in social media, and at the 4th Mendelian Randomization Conference. The checklist was then revised based on comments, further refined through 2020, and finalized in July 2021. Findings: The STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems. It covers both 1-sample and 2-sample MR studies that assess 1 or multiple exposures and outcomes, and addresses MR studies that follow a genome-wide association study and are reported in the same article. The checklist asks authors to justify why MR is a helpful method to address the study question and state prespecified causal hypotheses. The measurement, quality, and selection of genetic variants must be described and attempts to assess validi

Background: Escalating healthcare expenditures highlight the need to identify modifiable predictors of the use and costs of healthcare and sickness benefit transfers. We conducted a prospective analysis on Danish data to determine the costs associated with flourishing as compared to the below threshold level of flourishing. Methods: We used data from a 2016 Danish survey of 3508 adults, which was linked to Danish register data. Flourishing was assessed with a validated psychological well-being scale. A two-part regression model was used to predict 2017 costs while adjusting for 2016 costs, demographic variables, and health status, including psychiatric morbidity and health behaviours. Costs are expressed in USD PPP. Results: Applying criteria from prior literature, the prevalence of flourishing in Denmark (measured in 2016) was 34.7%. Flourishing was associated with significantly lower healthcare costs ($-687.7, 95% CI = $-1295.0, $-80.4) and sickness benefit transfers ($-297.8, 95% CI = $-551.5, $-44.0) per person in 2017, as compared to the below threshold level of flourishing. Extrapolated to the Danish population (4.1 M people aged 16+ years), flourishing was associated with lower healthcare costs and sickness benefit transfers amounting to $-1.2bn (95% CI = $-2.3 bn, $-149.0 M). Conclusions: Flourishing is associated with considerably lower health-related government expenditure. Substantial reductions could potentially be achieved by increasing the number of people who are flourishing in the population.

Background: Escalating healthcare expenditures highlight the need to identify modifiable predictors of the use and costs of healthcare and sickness benefit transfers. We conducted a prospective analysis on Danish data to determine the costs associated with flourishing as compared to the below threshold level of flourishing. Methods: We used data from a 2016 Danish survey of 3508 adults, which was linked to Danish register data. Flourishing was assessed with a validated psychological well-being scale. A two-part regression model was used to predict 2017 costs while adjusting for 2016 costs, demographic variables, and health status, including psychiatric morbidity and health behaviours. Costs are expressed in USD PPP. Results: Applying criteria from prior literature, the prevalence of flourishing in Denmark (measured in 2016) was 34.7%. Flourishing was associated with significantly lower healthcare costs ($-687.7, 95% CI = $-1295.0, $-80.4) and sickness benefit transfers ($-297.8, 95% CI = $-551.5, $-44.0) per person in 2017, as compared to the below threshold level of flourishing. Extrapolated to the Danish population (4.1 M people aged 16+ years), flourishing was associated with lower healthcare costs and sickness benefit transfers amounting to $-1.2bn (95% CI = $-2.3 bn, $-149.0 M). Conclusions: Flourishing is associated with considerably lower health-related government expenditure. Substantial reductions could potentially be achieved by increasing the number of people who are flourishing in the population.

Importance: Mendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias from confounding and reverse causation. Objective: To develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies. Design, Setting, and Participants: The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design users, developers of previous reporting guidelines, and journal editors, participated in a workshop in May 2019 to define the scope of the Statement and draft the checklist. The draft checklist was published as a preprint in July 2019 and discussed on the preprint platform, in social media, and at the 4th Mendelian Randomization Conference. The checklist was then revised based on comments, further refined through 2020, and finalized in July 2021. Findings: The STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems. It covers both 1-sample and 2-sample MR studies that assess 1 or multiple exposures and outcomes, and addresses MR studies that follow a genome-wide association study and are reported in the same article. The checklist asks authors to justify why MR is a helpful method to address the study question and state prespecified causal hypotheses. The measurement, quality, and selection of genetic variants must be described and attempts to assess validi

Mendelian randomisation (MR) studies allow a better understanding of the causal effects of modifiable exposures on health outcomes, but the published evidence is often hampered by inadequate reporting. Reporting guidelines help authors effectively communicate all critical information about what was done and what was found. STROBE-MR (strengthening the reporting of observational studies in epidemiology using mendelian randomisation) assists authors in reporting their MR research clearly and transparently. Adopting STROBE-MR should help readers, reviewers, and journal editors evaluate the quality of published MR studies. This article explains the 20 items of the STROBE-MR checklist, along with their meaning and rationale, using terms defined in a glossary. Examples of transparent reporting are used for each item to illustrate best practices.

Daniel Bos,1–3,* Arjola Bano,2,4,5,* Albert Hofman,1,2 Tyler J VanderWeele,1 Maryam Kavousi,2 Oscar H Franco,2 Meike W Vernooij,2,3 Robin P Peeters,2,4,5 M Arfan Ikram,1,2 Layal Chaker,1,2,4,5 1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 2Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; 3Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; 4Academic Center for Thyroid Diseases, Erasmus MC, Rotterdam, The Netherlands; 5Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands *These authors contributed equally to this work Background: The underlying mechanism of the association between thyroid function and atrial fibrillation (AF) is poorly understood, but epicardial adipose tissue (EAT) could be a promising mediator.Methods: In the 1995 participants (mean age 64.5 years) from the population-based Rotterdam Study, we measured thyroid function (thyroid-stimulating hormone, free thyroxine [FT4]) and performed computed tomography to quantify EAT volumes. All participants were followed for the occurrence of AF. We assessed associations of thyroid-stimulating hormone and FT4 with EAT and AF and performed causal mediation analysis to decompose the overall effect of thyroid function on AF with EAT as mediator.Results: Higher FT4 levels were associated with larger EAT volumes in persons with large waist circumferences, defined by sex-specific cutoffs (0.08 mL more EAT per 1-SD increase in FT4, 95% CI: 0.02, 0.14), but not in persons with a normal waist circumference. In persons with a large waist circumference, higher FT4 levels were associated with a higher AF risk (hazard ratio 1.50, 95% CI: 1.22, 1.83). We found no evidence of a mediating role of EAT in the association of thyroid function with AF (mediated interaction 1.6%, pure indirect effect 3.2%). The estimate of reference interaction of EAT with thyroid function on AF risk was more substantial (10.8

It is often of interest to decompose the total effect of an exposure into a component that acts on the outcome through some mediator and a component that acts independently through other pathways. Said another way, we are interested in the direct and indirect effects of the exposure on the outcome. Even if the exposure is randomly assigned, it is often infeasible to randomize the mediator, leaving the mediator-outcome confounding not fully controlled. We develop a sensitivity analysis technique that can bound the direct and indirect effects without parametric assumptions about the unmeasured mediator-outcome confounding.

It is often of interest to decompose the total effect of an exposure into a component that acts on the outcome through some mediator and a component that acts independently through other pathways. Said another way, we are interested in the direct and indirect effects of the exposure on the outcome. Even if the exposure is randomly assigned, it is often infeasible to randomize the mediator, leaving the mediator-outcome confounding not fully controlled. We develop a sensitivity analysis technique that can bound the direct and indirect effects without parametric assumptions about the unmeasured mediator-outcome confounding.

Background: Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited.

Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 x 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.

Consider the causal effect that one individual's treatment may have on another individual's outcome when the outcome is contagious, with specific application to the effect of vaccination on an infectious disease outcome. The effect of one individual's vaccination on another's outcome can be decomposed into two different causal effects, called the "infectiousness" and "contagion" effects. We present identifying assumptions and estimation or testing procedures for infectiousness and contagion effects in two different settings: (1) using data sampled from independent groups of observations, and (2) using data collected from a single interdependent social network. The methods that we propose for social network data require fitting generalized linear models (GLMs). GLMs and other statistical models that require independence across subjects have been used widely to estimate causal effects in social network data, but, because the subjects in networks are presumably not independent, the use of such models is generally invalid, resulting in inference that is expected to be anticonservative. We introduce a way to ensure that GLM residuals are uncorrelated across subjects despite the fact that outcomes are non-independent. This simultaneously demonstrates the possibility of using GLMs and related statistical models for network data and highlights their limitations., Comment: 28 pages

The causal inference literature has provided a clear formal definition of confounding expressed in terms of counterfactual independence. The literature has not, however, come to any consensus on a formal definition of a confounder, as it has given priority to the concept of confounding over that of a confounder. We consider a number of candidate definitions arising from various more informal statements made in the literature. We consider the properties satisfied by each candidate definition, principally focusing on (i) whether under the candidate definition control for all "confounders" suffices to control for "confounding" and (ii) whether each confounder in some context helps eliminate or reduce confounding bias. Several of the candidate definitions do not have these two properties. Only one candidate definition of those considered satisfies both properties. We propose that a "confounder" be defined as a pre-exposure covariate C for which there exists a set of other covariates X such that effect of the exposure on the outcome is unconfounded conditional on (X,C) but such that for no proper subset of (X,C) is the effect of the exposure on the outcome unconfounded given the subset. We also provide a conditional analogue of the above definition; and we propose a variable that helps reduce bias but not eliminate bias be referred to as a "surrogate confounder." These definitions are closely related to those given by Robins and Morgenstern [Comput. Math. Appl. 14 (1987) 869-916]. The implications that hold among the various candidate definitions are discussed., Comment: Published in at http://dx.doi.org/10.1214/12-AOS1058 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org)

Identifying effects of actions (treatments) on outcome variables from observational data and causal assumptions is a fundamental problem in causal inference. This identification is made difficult by the presence of confounders which can be related to both treatment and outcome variables. Confounders are often handled, both in theory and in practice, by adjusting for covariates, in other words considering outcomes conditioned on treatment and covariate values, weighed by probability of observing those covariate values. In this paper, we give a complete graphical criterion for covariate adjustment, which we term the adjustment criterion, and derive some interesting corollaries of the completeness of this criterion., Comment: Appears in Proceedings of the Twenty-Sixth Conference on Uncertainty in Artificial Intelligence (UAI2010)

COVID-19 has infected millions of people and upended the lives of most humans on the planet. Researchers from across the psychological sciences have sought to document and investigate the impact of COVID-19 in myriad ways, causing an explosion of research that is broad in scope, varied in methods, and challenging to consolidate. Because policy and practice aimed at helping people live healthier and happier lives requires insight from robust patterns of evidence, this article provides a rapid and thorough summary of high-quality studies available through early 2021 examining the mental-health consequences of living through the COVID-19 pandemic. Our review of the evidence indicates that anxiety, depression, and distress increased in the early months of the pandemic. Meanwhile, suicide rates, life satisfaction, and loneliness remained largely stable throughout the first year of the pandemic. In response to these insights, we present seven recommendations (one urgent, two short-term, and four ongoing) to support mental health during the pandemic and beyond.

Background: Escalating healthcare expenditures highlight the need to identify modifiable predictors of the use and costs of healthcare and sickness benefit transfers. We conducted a prospective analysis on Danish data to determine the costs associated with flourishing as compared to the below threshold level of flourishing. Methods: We used data from a 2016 Danish survey of 3508 adults, which was linked to Danish register data. Flourishing was assessed with a validated psychological well-being scale. A two-part regression model was used to predict 2017 costs while adjusting for 2016 costs, demographic variables, and health status, including psychiatric morbidity and health behaviours. Costs are expressed in USD PPP. Results: Applying criteria from prior literature, the prevalence of flourishing in Denmark (measured in 2016) was 34.7%. Flourishing was associated with significantly lower healthcare costs ($-687.7, 95% CI = $-1295.0, $-80.4) and sickness benefit transfers ($-297.8, 95% CI = $-551.5, $-44.0) per person in 2017, as compared to the below threshold level of flourishing. Extrapolated to the Danish population (4.1 M people aged 16+ years), flourishing was associated with lower healthcare costs and sickness benefit transfers amounting to $-1.2bn (95% CI = $-2.3 bn, $-149.0 M). Conclusions: Flourishing is associated with considerably lower health-related government expenditure. Substantial reductions could potentially be achieved by increasing the number of people who are flourishing in the population.