Decomposing heritability and genetic covariance by direct and indirect effect paths.

Estimation of heritability and genetic covariance is crucial for quantifying and understanding complex trait genetic architecture and is employed in almost all recent genome-wide association studies (GWAS). However, many existing approaches for heritability estimation and almost all methods for estimating genetic correlation ignore the presence of indirect genetic effects, i.e., genotype-phenotype associations confounded by the parental genome and family environment, and may thus lead to incorrect interpretation especially for human sociobehavioral phenotypes. In this work, we introduce a statistical framework to decompose heritability and genetic covariance into multiple components representing direct and indirect effect paths. Applied to five traits in UK Biobank, we found substantial involvement of indirect genetic components in shared genetic architecture across traits. These results demonstrate the effectiveness of our approach and highlight the importance of accounting for indirect effects in variance component analysis of complex traits.

GWAS on birth year infant mortality rates provides evidence of recent natural selection.

Following more than a century of phenotypic measurement of natural selection processes, much recent work explores relationships between molecular genetic measurements and realized fitness in the next generation. We take an innovative approach to the study of contemporary selective pressure by examining which genetic variants are "sustained" in populations as mortality exposure increases. Specifically, we deploy a so-called "regional GWAS" (genome-wide association study) that links the infant mortality rate (IMR) by place and year in the United Kingdom with common genetic variants among birth cohorts in the UK Biobank. These cohorts (born between 1936 and 1970) saw a decline in IMR from above 65 to under 20 deaths per 1,000 live births, with substantial subnational variations and spikes alongside wartime exposures. Our results show several genome-wide significant loci, including LCT and TLR10/1/6, related to area-level cohort IMR exposure during gestation and infancy. Genetic correlations are found across multiple domains, including fertility, cognition, health behaviors, and health outcomes, suggesting an important role for cohort selection in modern populations.

A quantile integral linear model to quantify genetic effects on phenotypic variability.

Detecting genetic variants associated with the variance of complex traits, that is, variance quantitative trait loci (vQTLs), can provide crucial insights into the interplay between genes and environments and how they jointly shape human phenotypes in the population. We propose a quantile integral linear model (QUAIL) to estimate genetic effects on trait variability. Through extensive simulations and analyses of real data, we demonstrate that QUAIL provides computationally efficient and statistically powerful vQTL mapping that is robust to non-Gaussian phenotypes and confounding effects on phenotypic variability. Applied to UK Biobank (n = 375,791), QUAIL identified 11 vQTLs for body mass index (BMI) that have not been previously reported. Top vQTL findings showed substantial enrichment for interactions with physical activities and sedentary behavior. Furthermore, variance polygenic scores (vPGSs) based on QUAIL effect estimates showed superior predictive performance on both population-level and within-individual BMI variability compared to existing approaches. Overall, QUAIL is a unified framework to quantify genetic effects on the phenotypic variability at both single-variant and vPGS levels. It addresses critical limitations in existing approaches and may have broad applications in future gene-environment interaction studies.

The effects of education on mortality: Evidence using college expansions.

This paper explores the long-run health benefits of education for longevity. Using mortality data from the Social Security Administration (1988-2005) linked to geographic locations in the 1940-census data, we exploit changes in college availability across cohorts in local areas. Our treatment on the treated calculations suggest increases in longevity between 1.3 and 2.7 years. Some further analyses suggest the results are not driven by pre-tends, endogenous migration, and other time-varying local confounders. This paper adds to the literature on the health and social benefits of education.

Dust to Feed, Dust to Gray: The Effect of in Utero Exposure to the Dust Bowl on Old-Age Longevity.

Intensive agriculture and deep plowing caused topsoil erosion and dust storms during the 1930s, affecting agricultural income and land values for years. Given the growing literature on the relevance of in utero and early-life exposures, it is surprising that studies focusing on links between the Dust Bowl and later-life health have produced inconclusive and mixed results. We reevaluate this literature and study the long-term effects of in utero and early-life exposure to topsoil erosion caused by the 1930s Dust Bowl on old-age longevity. Specifically, using Social Security Administration death records linked with the full-count 1940 census, we conduct event studies with difference-in-differences designs to compare the longevity of individuals in high- versus low-topsoil-erosion counties before versus after 1930. We find intent-to-treat reductions in longevity of approximately 0.85 months for those born in high-erosion counties after 1930. We show that these effects are not an artifact of preexisting trends in longevity. Additional analyses suggest that the effects are more pronounced among children raised in farm households, females, and those whose mothers had lower education. We also provide suggestive evidence that reductions in adulthood income are a likely mechanism for the effects we document.

Retirement Makes You Old? Causal Effect of Retirement on Biological Age.

Retirement is a critical life event for older people. Health scholars have scrutinized the health effects of retirement, but its consequences on age-related diseases and mortality are unclear. We extend this body of research by integrating measurements of biological age, representing the physiological decline preceding disease onset. Using data from the UK Biobank and a fuzzy regression discontinuity design, we estimated the effects of retirement on two biomarker-based biological age measures. Results showed that retirement significantly increases biological age for those induced to retire by the State Pension eligibility by 0.871-2.503 years, depending on sex and specific biological age measurement. Given the emerging scientific discussion about direct interventions to biological age to achieve additional improvements in population health, the positive effect of retirement on biological age has important implications for an increase in the State Pension eligibility age and its potential consequences on population health, public health care policy, and older people's labor force participation. Overall, this study provides novel empirical evidence contributing to the question of what social factors make people old.

Separating Scarring Effect and Selection of Early-Life Exposures With Genetic Data.

Causal life course research examining consequences of early-life exposures has largely relied on associations between early-life environments and later-life outcomes using exogenous environmental shocks. Nonetheless, even with (quasi-)randomized early-life exposures, these associations may reflect not only causation ("scarring") but also selection (i.e., which members are included in data assessing later life). Investigating this selection and its impacts on estimated effects of early-life conditions has, however, often been ignored because of a lack of pre-exposure data. This study proposes an approach for assessing and correcting selection, separately from scarring, using genetic measurements. Because genetic measurements are determined at the time of conception, any associations with early-life exposures should be interpreted as selection. Using data from the UK Biobank, we find that in utero exposure to a higher area-level infant mortality rate is associated with genetic predispositions correlated with better educational attainment and health. These findings point to the direction and magnitude of selection from this exposure. Corrections for this selection in examinations of effects of exposure on later educational attainment suggest underestimates of 26-74%; effects on other life course outcomes also vary across selection correction methods.

Cardiovascular Health in Black and Latino Adults With Type 2 Diabetes.

BACKGROUND: The incidence of type 2 diabetes (T2DM) among U.S. adults has been rising annually, with a higher incidence rate in Black and Hispanic adults than in Whites. The American Heart Association (AHA) has defined cardiovascular health according to the achievement of seven health behaviors (smoking, body mass index [BMI], physical activity, diet) and health factors (total cholesterol, blood pressure, fasting glucose). Optimal cardiovascular health has been associated with a lower risk of cardiovascular disease, and awareness of this risk may influence healthy behaviors. OBJECTIVES: This study aimed to assess cardiovascular health in a sample of Black and Hispanic adults (age: 18-40 years) with T2DM and explore the barriers and facilitators to diabetes self-management and cardiovascular health. METHODS: This was an explanatory sequential mixed-method design. The study staff recruited adults with T2DM for the quantitative data followed by qualitative interviews with a subsample of participants using maximum variation sampling. The seven indices of cardiovascular health as defined by the AHA's "Life's Simple 7" were assessed: health behaviors (smoking, BMI, physical activity, diet) and health factors (total cholesterol, blood pressure, A1C). Qualitative interviews were conducted to explore their results as well as the effects of the pandemic on diabetes self-management. Qualitative and quantitative data were integrated into the final analysis phase. RESULTS: The majority of the sample was female, with 63% identifying as Black and 47% as Hispanic. The factor with the lowest achievement of ideal levels was BMI, followed by a healthy diet. Less than half achieved ideal levels of blood pressure or physical activity. Themes that emerged from the qualitative data included the impact of social support, the effects of the pandemic on their lives, and educating themselves about T2DM. DISCUSSION: Achievement of ideal cardiovascular health factors varied, but the achievement of several health factors may be interrelated. Intervening on even one factor while providing social support may improve other areas of cardiovascular health in this population.

Estimating genetic nurture with summary statistics of multigenerational genome-wide association studies.

Marginal effect estimates in genome-wide association studies (GWAS) are mixtures of direct and indirect genetic effects. Existing methods to dissect these effects require family-based, individual-level genetic, and phenotypic data with large samples, which is difficult to obtain in practice. Here, we propose a statistical framework to estimate direct and indirect genetic effects using summary statistics from GWAS conducted on own and offspring phenotypes. Applied to birth weight, our method showed nearly identical results with those obtained using individual-level data. We also decomposed direct and indirect genetic effects of educational attainment (EA), which showed distinct patterns of genetic correlations with 45 complex traits. The known genetic correlations between EA and higher height, lower body mass index, less-active smoking behavior, and better health outcomes were mostly explained by the indirect genetic component of EA. In contrast, the consistently identified genetic correlation of autism spectrum disorder (ASD) with higher EA resides in the direct genetic component. A polygenic transmission disequilibrium test showed a significant overtransmission of the direct component of EA from healthy parents to ASD probands. Taken together, we demonstrate that traditional GWAS approaches, in conjunction with offspring phenotypic data collection in existing cohorts, could greatly benefit studies on genetic nurture and shed important light on the interpretation of genetic associations for human complex traits.

Unequal before death: The effect of paternal education on children's old-age mortality in the United States.

A growing body of research documents the relevance of parental education as a marker of family socio-economic status for children's later-life health outcomes. A strand of this literature evaluates how the early-life environment shapes mortality outcomes during infancy and childhood. However, the evidence on mortality during the life course and old age is limited. This paper contributes to the literature by analysing the association between paternal education and children's old-age mortality. We use data from Social Security Administration death records over the years 1988-2005 linked to the United States 1940 Census. Applying a family(cousin)- fixed-effects model to account for shared environment, childhood exposures, and common endowments that may confound the long-term links, we find that having a father with a college or high-school education, compared with elementary/no education, is associated with a 4.6- or 2.6-month-higher age at death, respectively, for the child, conditional on them surviving to age 47.

A Pilot Study Toward Development of the Digital Literacy, Usability, and Acceptability of Technology Instrument for Healthcare.

Electronic health record proficiency is critical for health professionals to deliver and document patient care. There is scarce research on this topic within undergraduate nursing student populations. The purpose of this study is to describe the psychometric evaluation of the Digital Literacy, Usability, and Acceptability of Technology Instrument for Healthcare. A cross-sectional pilot study for psychometric evaluation of the instrument was conducted using data collected through an emailed survey. Exploratory factor analysis, inter-item and adjusted item-total correlations, and Cronbach's α calculated subscale reliability. A total of 297 nursing students completed the survey. A seven-factor structure best fit the data: technology use-engagement, technology use-confidence, technology use-history, electronic health record-ease of use, electronic health record-comparability, and electronic health record-burden. Cronbach's α indicated good to very good internal consistency (α = .68 to .89). The instrument effectively measured digital literacy, acceptance, and usability of an electronic health record and may be implemented with good to very good reliability across varied healthcare simulation and training experiences.

Feasibility and Acceptability of the Adherence Connection Counseling, Education, and Support (ACCESS) Proof of Concept: A Peer-Led, Mobile Health (mHealth) Cognitive Behavioral Antiretroviral Therapy (ART) Adherence Intervention for HIV-Infected (HIV+) Adolescents and Young Adults (AYA).

Effective antiretroviral therapy (ART) adherence strategies for HIV+ adolescents and young adults (AYA) are needed to prevent HIV-related morbidity, mortality, and onward transmission. In the Adherence Connection for Counseling, Education, and Support (ACCESS) pilot, an exploratory sequential mixed-methods design was used to develop and test a peer-led, mobile health (mHealth) cognitive behavioral ART adherence intervention. HIV+ AYA (ages 16-29 years) with unsuppressed plasma HIV RNA (HIV viral load) were eligible for this five-session intervention directed to improving ART adherence and HIV viral load. A total of 78 peer-led remote videoconferencing sessions (via WebEx) were delivered to 16 participants. High completion rates (97.5%) and client satisfaction scores (mean = 29.13 of 32; SD = 2.45) were observed. Self-reported ART adherence improved (32% increase in doses taken; 95th CI 11.2-53.3) with an annualized average rate of 47.5% (0.28 log10) reduction in HIV viral load. We established proof of concept for the ACCESS peer-led, mHealth cognitive behavioral ART adherence intervention, with promising adherence and virologic outcome data.

RESUMEN: Se necesitan estrategias efectivas de adherencia a la terapia antirretroviral (TAR) para adolescentes y adultos jóvenes (AAJ) VIH+ para prevenir la morbilidad, la mortalidad y las transmisiones futuras relacionadas con el VIH. En el proyecto piloto Adherence Connection for Counseling, Education, and Support (ACCESS), se utilizó un diseño exploratorio secuencial de métodos mixtos para desarrollar y testear una intervención de adherencia cognitiva conductual de salud móvil (mHealth) dirigida por pares a la TAR. AAJ VIH+ (de 16 a 29 años de edad) con ARN del VIH (carga viral del VIH) en plasma no suprimido fueron elegibles para esta intervención de cinco sesiones dirigida a mejorar la adherencia a la TAR y la carga viral del VIH. Se dictaron un total de 78 sesiones de videoconferencias remotas dirigidas por pares (a través de WebEx) a 16 participantes. Fueron observadas tasas altas de finalización (97.5%) y puntuaciones de satisfacción del cliente (media=29.13 de 32; SD=2.45). La adherencia autoinformada a la TAR mejoró (aumento del 32% en las dosis tomadas; IC del 95=11.2 a 53.3) con una tasa promedio anualizada de reducción en la carga viral del VIH del 47.5% (0.28 log 10). Establecimos una prueba de concepto para ACCESS, la intervención de adherencia a la TAR cognitivo conductual mHealth dirigida por pares, con datos prometedores sobre la adherencia y los resultados virológicos.

Childhood exposure to birth registration laws and old-age mortality.

This paper studies the effects of the enactment of birth registration laws, as the official universal and uniform method of recording births, across US states in the first decades of the 20th century on old-age longevity for children affected by these laws. We show that establishing birth registration laws has long-term benefits for old-age health. The benefits are primarily driven by states with an effective child labor policy, suggesting that registering births helps the enforcement of child labor laws which in turn operate as the mechanism channel to improve old-age longevity. A treatment-on-treated calculation suggests an increase of 0.6 years of longevity from not working during childhood due to the birth registration law.

Understanding Geographic Disparities in Mortality.

A rich literature shows that early-life conditions shape later-life outcomes, including health and migration events. However, analyses of geographic disparities in mortality outcomes focus almost exclusively on contemporaneously measured geographic place (e.g., state of residence at death), thereby potentially conflating the role of early-life conditions, migration patterns, and effects of destinations. We employ the newly available Mortality Disparities in American Communities data set, which links respondents in the 2008 American Community Survey to official death records, and estimate consequential differences based on the method of aggregation we use: the unweighted mean absolute deviation of the difference in life expectancy at age 50 measured by state of birth versus state of residence is 0.58 years for men and 0.40 years for women. These differences are also spatially clustered, and we show that regional inequality in life expectancy is higher based on life expectancies by state of birth, implying that interstate migration mitigates baseline geographic inequality in mortality outcomes. Finally, we assess how state-specific features of in-migration, out-migration, and nonmigration together shape measures of mortality disparities by state (of residence), further demonstrating the difficulty of clearly interpreting these widely used measures.

The Big (Genetic) Sort? A Research Note on Migration Patterns and Their Genetic Imprint in the United Kingdom.

This research note reinvestigates Abdellaoui et al.'s (2019) findings that genetically selective migration may lead to persistent and accumulating socioeconomic and health inequalities between types (coal mining or non-coal mining) of places in the United Kingdom. Their migration measure classified migrants who moved to the same type of place (coal mining to coal mining or non-coal mining to non-coal mining) into "stay" categories, preventing them from distinguishing migrants from nonmigrants. We reinvestigate the question of genetically selective migration by examining migration patterns between places rather than place types and find genetic selectivity in whether people migrate and where. For example, we find evidence of positive selection: people with genetic variants correlated with better education moved from non-coal mining to coal mining places with our measure of migration. Such findings were obscured in earlier work that could not distinguish nonmigrants from migrants.

Understanding Internal Migration: A Research Note Providing an Assessment of Migration Selection With Genetic Data.

Migration is selective, resulting in inequalities between migrants and nonmigrants. However, investigating migration selection is empirically challenging because combined pre- and post-migration data are rarely available. We propose an alternative approach to assessing internal migration selection by integrating genetic data, enabling an investigation of migration selection with cross-sectional data collected post-migration. Using data from the UK Biobank, we utilized standard tools from statistical genetics to conduct a genome-wide association study (GWAS) for migration distance. We then calculated genetic correlations to compare GWAS results for migration with those for other characteristics. Given that individual genetics are determined at conception, these analyses allow a unique exploration of the association between pre-migration characteristics and migration. Results are generally consistent with the healthy migrant literature: genetics correlated with longer migration distance are associated with higher socioeconomic status and better health. We also extended the analysis to 53 traits and found novel correlations between migration and several physical health, mental health, personality, and sociodemographic traits.

Integrative Review of Methods From Youth Risk Behavior Survey Secondary Data Analyses Examining HIV Syndemic Factors Among Adolescent Gay and Bisexual Men.

BACKGROUND: Adolescent gay/bisexual men exhibit the highest prevalence of undiagnosed HIV infections. Ascertaining antecedents of behaviorally acquired HIV infections among adolescent gay/bisexual men can be challenging; however, these challenges can be overcome through the utilization of secondary data, such as the Youth Risk Behavior Survey. OBJECTIVE: Syndemics theory suggests that HIV infections are not a singular phenomenon; instead, many infections occur at the intersection of syndemic factors, such as substance use, violence, and mental health. Our objective is to describe and synthesize research methods of secondary data analyses that examine syndemic factors in relation to HIV risk behavior outcomes among subsamples of adolescent gay/bisexual men. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycInfo were systematically searched. Inclusion criteria were (a) peer-reviewed Youth Risk Behavior Survey secondary data analyses conducted in the United States after 1991, (b) subsamples with adolescent gay/bisexual men, (c) one or more syndemic factor(s), and (d) one or more HIV risk behavior outcome(s). We used the National Institutes of Health Quality Assessment Tools for quality appraisal. RESULTS: Of 1,036 citations retrieved, nine studies met inclusion criteria. Results included using logistic regression analysis and data from 2015 to 2017 in six studies and underpinnings with minority stress theory in four studies. Eight studies omitted race/ethnicity in subsamples and six grouped lesbians with adolescent gay/bisexual men. Seven studies examined substance use, six examined violence, and five examined mental health. Condom use and number of partners were the most studied HIV risk behavior outcomes in four studies, whereas intercourse in the last 3 months was an outcome in only one study. Protective factors were not present. CONCLUSION: Limitations found the need to highlight better inclusion of race/ethnicity and sexual orientation. Adding contemporary survey items is also necessary, such as nonbinary sex and gender identity, access to HIV prevention (condoms, HIV testing, and preexposure prophylaxis), and experiences with stigma, to elucidate risk behaviors among populations disproportionately affected by HIV infections, including Blacks/African Americans and Hispanics/Latinos.

The Impact of an Electronic Best Practice Advisory on Patients' Physical Activity and Cardiovascular Risk Profile.

BACKGROUND: Regular physical activity (PA) is a component of cardiovascular health and is associated with a lower risk of cardiovascular disease (CVD). However, only about half of US adults achieved the current PA recommendations. OBJECTIVE: The study purpose was to implement PA counseling using a clinical decision support tool in a preventive cardiology clinic and to assess changes in CVD risk factors in a sample of patients enrolled over 12 weeks of PA monitoring. METHODS: This intervention, piloted for 1 year, had 3 components embedded in the electronic health record: assessment of patients' PA, an electronic prompt for providers to counsel patients reporting low PA, and patient monitoring using a Fitbit. Cardiovascular disease risk factors included PA (self-report and Fitbit), body mass index, blood pressure, lipids, and cardiorespiratory fitness assessed with the 6-minute walk test. Depression and quality of life were also assessed. Paired t tests assessed changes in CVD risk. RESULTS: The sample who enrolled in the remote patient monitoring (n = 59) were primarily female (51%), White adults (76%) with a mean age of 61.13 ± 11.6 years. Self-reported PA significantly improved over 12 weeks (P = .005), but not Fitbit steps (P = .07). There was a significant improvement in cardiorespiratory fitness (469 ± 108 vs 494 ± 132 m, P = .0034), and 23 participants (42%) improved at least 25 m, signifying a clinically meaningful improvement. Only 4 participants were lost to follow-up over 12 weeks of monitoring. CONCLUSIONS: Patients may need more frequent reminders to be active after an initial counseling session, perhaps getting automated messages based on their step counts syncing to their electronic health record.

Often wrong, sometimes useful: Including polygenic scores in social science research.

This commentary seeks to briefly outline a clear-eyed middle ground between Burt's claims that the inclusion of polygenic scores (PGSs) is essentially useless for social science and proponents' vast overstatements and over-interpretations of these scores. Current practice of including PGSs in social science is often wrong but sometimes useful.

Hospital characteristics associated with nurse staffing during labor and birth: Inequities for the most vulnerable maternity patients.

BACKGROUND: Evidence is limited on nurse staffing in maternity units. PURPOSE: To estimate the relationship between hospital characteristics and adherence with Association of Women's Health, Obstetric and Neonatal Nurses nurse staffing guidelines. METHODS: We enrolled 3,471 registered nurses in a cross-sectional survey and obtained hospital characteristics from the 2018 American Hospital Association Annual Survey. We used mixed-effects linear regression models to estimate associations between hospital characteristics and staffing guideline adherence. FINDINGS: Overall, nurses reported strong adherence to AWHONN staffing guidelines (rated frequently or always met by ≥80% of respondents) in their hospitals. Higher birth volume, having a neonatal intensive care unit, teaching status, and higher percentage of births paid by Medicaid were all associated with lower mean guideline adherence scores. DISCUSSION AND CONCLUSIONS: Important gaps in staffing were reported more frequently at hospitals serving patients more likely to have medical or obstetric complications, leaving the most vulnerable patients at risk.