Genetic influences on depression and selection into adverse life experiences.

Genome-wide association studies find that a large number of genetic variants jointly influence the risk of depression, which is summarized by polygenic indices (PGIs) of depressive symptoms and major depression. But PGIs by design remain agnostic about the causal mechanisms linking genes to depression. Meanwhile, the role of adverse life experiences in shaping depression risk is well-documented, including via gene-environment correlation. Building on theoretical work on dynamic and contingent genetic selection, we suggest that genetic influences may lead to differential selection into negative life experiences, forging gene-environment correlations that manifest in various permutations of depressive behaviors and environmental adversities. We also examine the extent to which apparent genetic influences may reflect spurious associations due to factors such as indirect genetic effects. Using data from two large surveys of middle-aged and older US adults, we investigate to what extent a PGI of depression predicts the risk of 27 different adversities. Further, to glean insights about the kinds of processes that might lead to gene-environment correlation, we augment these analyses with data from an original preregistered survey to measure cultural understandings of the behavioral dependence of various adversities. We find that the PGI predicts the risk of majority of adversities, net of class background and prior depression, and that the selection risk is greater for adversities typically perceived as being dependent on peoples' own behaviors. Taken together, our findings suggest that the PGI of depression largely picks up the risk of behaviorally-influenced adversities, but to a lesser degree also captures other environmental influences. The results invite further exploration into the behavioral and interactional processes that lie along the pathways intervening between genetic differences and wellbeing.

Mechanism substitution in preventive innovations: Dissecting the reproduction of health inequalities in the United States.

In the last three decades, numerous studies in different countries have corroborated the main postulates of the Fundamental Cause Theory (FCT), providing evidence showing how health inequalities are reproduced as society increases its capacity to control disease and/or avoid its consequences through preventive innovations. However, documenting the reproductive logic proposed by the theory requires the development of a dynamic analytical approach to consider socioeconomic disparities in the incorporation of multiple preventive innovations over time, which could act as mediating mechanisms of the durable relationship between socioeconomic status and health/mortality. This study draws on data from different waves of the National Health Interview Survey and the National Health and Nutrition Examination Survey to analyze the diffusion processes of various innovations in the U.S. The results of the study show that educational inequalities emerge, are amplified, and are reduced by the continuous diffusion of preventive innovations, supporting the meta-hypothesis of substitution of mediating mechanisms according to the interconnections of FCT and Diffusion of Innovation Theory.

Wrestling with Social and Behavioral Genomics: Risks, Potential Benefits, and Ethical Responsibility.

In this consensus report by a diverse group of academics who conduct and/or are concerned about social and behavioral genomics (SBG) research, the authors recount the often-ugly history of scientific attempts to understand the genetic contributions to human behaviors and social outcomes. They then describe what the current science-including genomewide association studies and polygenic indexes-can and cannot tell us, as well as its risks and potential benefits. They conclude with a discussion of responsible behavior in the context of SBG research. SBG research that compares individuals within a group according to a "sensitive" phenotype requires extra attention to responsible conduct and to responsible communication about the research and its findings. SBG research (1) on sensitive phenotypes that (2) compares two or more groups defined by (a) race, (b) ethnicity, or (c) genetic ancestry (where genetic ancestry could easily be misunderstood as race or ethnicity) requires a compelling justification to be conducted, funded, or published. All authors agree that this justification at least requires a convincing argument that a study's design could yield scientifically valid results; some authors would additionally require the study to have a socially favorable risk-benefit profile.

Variation in initial and continued use of primary, mental health, and specialty video care among Veterans.

OBJECTIVE: To identify which Veteran populations are routinely accessing video-based care. DATA SOURCES AND STUDY SETTING: National, secondary administrative data from electronic health records at the Veterans Health Administration (VHA), 2019-2021. STUDY DESIGN: This retrospective cohort analysis identified patient characteristics associated with the odds of using any video care; and then, among those with a previous video visit, the annual rate of video care utilization. Video care use was reported overall and stratified into care type (e.g., primary, mental health, and specialty video care) between March 10, 2020 and February 28, 2021. DATA COLLECTION: Veterans active in VA health care (>1 outpatient visit between March 11, 2019 and March 10, 2020) were included in this study. PRINCIPAL FINDINGS: Among 5,389,129 Veterans in this evaluation, approximately 27.4% of Veterans had at least one video visit. We found differences in video care utilization by type of video care: 14.7% of Veterans had at least one primary care video visit, 10.6% a mental health video visit, and 5.9% a specialty care video visit. Veterans with a history of housing instability had a higher overall rate of video care driven by their higher usage of video for mental health care compared with Veterans in stable housing. American Indian/Alaska Native Veterans had reduced odds of video visits, yet similar rates of video care when compared to White Veterans. Low-income Veterans had lower odds of using primary video care yet slightly elevated rates of primary video care among those with at least one video visit when compared to Veterans enrolled at VA without special considerations. CONCLUSIONS: Variation in video care utilization patterns by type of care identified Veteran populations that might require greater resources and support to initiate and sustain video care use. Our data support service specific outreach to homeless and American Indian/Alaska Native Veterans.

Advances in transparency and reproducibility in the social sciences.

Worries about a "credibility crisis" besieging science have ignited interest in research transparency and reproducibility as ways of restoring trust in published research. For quantitative social science, advances in transparency and reproducibility can be seen as a set of developments whose trajectory predates the recent alarm. We discuss several of these developments, including preregistration, data-sharing, formal infrastructure in the form of resources and policies, open access to research, and specificity regarding research contributions. We also discuss the spillovers of this predominantly quantitative effort towards transparency for qualitative research. We conclude by emphasizing the importance of mutual accountability for effective science, the essential role of openness for this accountability, and the importance of scholarly inclusiveness in figuring out the best ways for openness to be accomplished in practice.

Cognitive Capacity Genome-Wide Polygenic Scores Identify Individuals with Slower Cognitive Decline in Aging.

The genetic protective factors for cognitive decline in aging remain unknown. Predicting an individual's rate of cognitive decline-or with better cognitive resilience-using genetics will allow personalized intervention for cognitive enhancement and the optimal selection of target samples in clinical trials. Here, using genome-wide polygenic scores (GPS) of cognitive capacity as the genomic indicators for variations of human intelligence, we analyzed the 18-year records of cognitive and behavioral data of 8511 European-ancestry adults from the Wisconsin Longitudinal Study (WLS), specifically focusing on the cognitive assessments that were repeatedly administered to the participants with their average ages of 64.5 and 71.5. We identified a significant interaction effect between age and cognitive capacity GPS, which indicated that a higher cognitive capacity GPS significantly correlated with a slower cognitive decline in the domain of immediate memory recall (ß = 1.86 × 10-1, p-value = 1.79 × 10-3). The additional phenome-wide analyses identified several associations between cognitive capacity GPSs and cognitive/behavioral phenotypes, such as similarities task (ß = 1.36, 95% CI = (1.22, 1.51), p-value = 3.59 × 10-74), number series task (ß = 0.94, 95% CI = (0.85, 1.04), p-value = 2.55 × 10-78), IQ scores (ß = 1.42, 95% CI = (1.32, 1.51), p-value = 7.74 × 10-179), high school classrank (ß = 1.86, 95% CI = (1.69, 2.02), p-value = 3.07 × 10-101), Openness from the BIG 5 personality factor (p-value = 2.19 × 10-14, ß = 0.57, 95% CI = (0.42, 0.71)), and leisure activity of reading books (ß = 0.50, 95% CI = (0.40, 0.60), p-value = 2.03 × 10-21), attending cultural events, such as concerts, plays, or museums (ß = 0.60, 95% CI = (0.49, 0.72), p-value = 2.06 × 10-23), and watching TV (ß = -0.48, 95% CI = (-0.59, -0.37), p-value = 4.16 × 10-18). As the first phenome-wide analysis of cognitive and behavioral phenotypes, this study presents the novel genetic protective effects of cognitive ability on the decline of memory recall in an aging population.

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals.

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

Birth order differences in education originate in postnatal environments.

Siblings share many environments and much of their genetics. Yet, siblings turn out different. Intelligence and education are influenced by birth order, with earlier-born siblings outperforming later-borns. We investigate whether birth order differences in education are caused by biological differences present at birth, that is, genetic differences or in utero differences. Using family data that spans two generations, combining registry, survey, and genotype information, this study is based on the Norwegian Mother, Father, and Child Cohort Study (MoBa). We show that there are no genetic differences by birth order as captured by polygenic scores (PGSs) for educational attainment. Earlier-born have lower birth weight than later-born, indicating worse uterine environments. Educational outcomes are still higher for earlier-born children when we adjust for PGSs and in utero variables, indicating that birth order differences arise postnatally. Finally, we consider potential environmental influences, such as differences according to maternal age, parental educational attainment, and sibling genetic nurture. We show that birth order differences are not biological in origin, but pinning down their specific causes remains elusive.

Resource profile and user guide of the Polygenic Index Repository.

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs' prediction accuracies, we constructed them using genome-wide association studies-some not previously published-from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the 'additive SNP factor'. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.

The diffusion of innovative diabetes technologies as a fundamental cause of social inequalities in health. The Nord-Trøndelag Health Study, Norway.

This study investigates patterns of adoption and diffusion of innovative health technologies by socioeconomic status (SES) in order to assess the extent to which these technologies may be a fundamental cause of health-related inequalities. Quantitative analyses examined SES-based inequalities in the adoption and diffusion of diabetes technologies. Diabetes data from three panels of the Nord-Trøndelag Health Study (HUNT), Norway, were combined with income and education data. Cross-sectional and longitudinal regression analyses were used to examine relevant inequalities. Cross-sectional analyses suggest often present SES-based gradients in the adoption of diabetes technologies, favouring high-SES groups. Statistically significant differences (p ≤ 0.05) were most often present when technologies were new. In a cohort followed from 1984 to 1997, high SES individuals were more likely to adopt insulin injection technologies but, due to modest sample sizes, these inequalities were not statistically significant after adjusting for age, gender, and duration of illness. Moreover, compared to low SES individuals, high SES individuals are more active users of diabetes technologies. Results suggest that SES-based variations in access and use of innovative health technologies could act as a mechanism through which inequalities are reproduced. This study provides a discussion of mechanisms and a methodological foundation for further investigation.

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences.

Differential fertility makes society more conservative on family values.

Data from the General Social Survey indicate that higher-fertility individuals and their children are more conservative on "family values" issues, especially regarding abortion and same-sex marriage. This pattern implies that differential fertility has increased and will continue to increase public support for conservative policies on these issues. The association of family size with conservatism is specific to traditional-family issues and can be attributed in large part to the greater religiosity and lower educational attainment of individuals from larger families. Over the 2004 to 2018 period, opposition to same-sex marriage and abortion was 3 to 4 percentage points more prevalent than it would have been were traditional-family conservatism independent of family size in the current generation. For same-sex marriage, evolutionary forces have grown in relative importance as society as a whole has liberalized. As of 2018, differential fertility raised the number of US adults opposed to same-sex marriage by 17%, from 46.9 million to 54.8 million.

Networks of problems: social, psychological, and genetic influences on health.

An emerging idea in psychopathology conceives of disorders as networks of mutually-reinforcing symptoms that constitute the disorder rather than simply reflect it. This is similar to how social scientists already view socioeconomic status, and has affinities to how physical health problems compound in later life. Social, psychological, and physical conditions might therefore be thought of as networks of problems with 'causal bridges' that span different levels and bring low SES, mental health challenges, and physical health problems into pervasive relationships with one another. The network view suggests a more heterogeneous and less reductive view on genetic causes which accords with the highly diffuse causal architecture now known to be the hallmark of complex behaviors and traits.

Genetic analysis of social-class mobility in five longitudinal studies.

A summary genetic measure, called a "polygenic score," derived from a genome-wide association study (GWAS) of education can modestly predict a person's educational and economic success. This prediction could signal a biological mechanism: Education-linked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents' position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother's polygenic score predicted her child's attainment over and above the child's own polygenic score, suggesting parents' genetics can also affect their children's attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals' family-of-origin environments and their social mobility.

Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

Schools as Moderators of Genetic Associations with Life Course Attainments: Evidence from the WLS and Add Health.

Genetic variants identified in genome-wide association studies of educational attainment have been linked with a range of positive life course development outcomes. However, it remains unclear whether school environments may moderate these genetic associations. We analyze data from two biosocial surveys that contain both genetic data and follow students from secondary school through mid- to late life. We test if the magnitudes of the associations with educational and occupational attainments varied across the secondary schools that participants attended or with characteristics of those schools. Although we find little evidence that genetic associations with educational and occupational attainment varied across schools or with school characteristics, genetic associations with any postsecondary education and college completion were moderated by school-level socioeconomic status. Along similar lines, we observe substantial between-school variation in the average level of educational attainment students achieved for a fixed genotype. These findings emphasize the importance of social context in the interpretation of genetic associations. Specifically, our results suggest that though existing measures of individual genetic endowment have a linear relationship with years of schooling that is relatively consistent across school environments, school context is crucial in connecting an individual's genotype to his or her likelihood of crossing meaningful educational thresholds.

Socioeconomic status and genetic influences on cognitive development.

Accurate understanding of environmental moderation of genetic influences is vital to advancing the science of cognitive development as well as for designing interventions. One widely reported idea is increasing genetic influence on cognition for children raised in higher socioeconomic status (SES) families, including recent proposals that the pattern is a particularly US phenomenon. We used matched birth and school records from Florida siblings and twins born in 1994-2002 to provide the largest, most population-diverse consideration of this hypothesis to date. We found no evidence of SES moderation of genetic influence on test scores, suggesting that articulating gene-environment interactions for cognition is more complex and elusive than previously supposed.

Fundamental causes of accelerated declines in colorectal cancer mortality: Modeling multiple ways that disadvantage influences mortality risk.

BACKGROUND: Improvements in colorectal cancer (CRC) mortality reflect the distribution of effective preventions. Social inequalities often generate unequal diffusion of medical interventions, resulting in disparate outcomes while preventions are being disseminated throughout the population. This study used a novel method to examine whether Race (Black versus White) and SES influenced when rates of CRC mortality started to decline, and how rapidly they did so. METHOD: Mortality counts from 1968-2010 were derived from death certificates of U.S. residents aged 25 + years. Individuals' race, age, county of residence, and sex were collected from death certificates. County-level SES was measured using the decennial U.S. census. Layered joinpoint regression was used to model CRC mortality trends over time. Acceleration in rates of historical decline were used to indicate preventability within counties. RESULTS: Black race was associated with a 4.1-year delay in colonoscopy-attributable declines in CRC mortality and each standard deviation unit change in SES with a 5.7-year delay in such mortality. Following the onset of a decline, colonoscopy-attributable mortality change was slower by 0.5% among Blacks, and 2.0%/standard deviation in SES. Modifying the rapidity of colonoscopy uptake could have averted 12-14,000 and 83-86,000 deaths among Blacks and residents of lower SES counties, respectively. CONCLUSIONS: Successful interventions do not uniformly benefit the U.S. POPULATION: This study highlighted the notable impact that substantial delays in the provision of interventions, and in the relative rapidity of dissemination, and estimated the extent to which there was a preventable loss of life concentrated amongst the most disadvantaged. A more egalitarian delivery of life-saving interventions could drastically reduce mortality by improving effectiveness of interventions while also addressing inequalities in health.

Shared Environment Estimates for Educational Attainment: A Puzzle and Possible Solutions.

Classical behavioral genetics models for twin and other family designs decompose traits into heritability, shared environment, and nonshared environment components. Estimates of heritability of adult traits are pervasively observed to be far higher than those of shared environment, which has been used to make broad claims about the impotence of upbringing. However, the most commonly studied nondemographic variable in many areas of social science, educational attainment, exhibits robustly high estimates both for heritability and for shared environment. When previously noticed, the usual explanation has emphasized family resources, but evidence suggests this is unlikely to explain the anomalous high estimates for shared environment of educational attainment. We articulate eight potential complementary explanations and discuss evidence of their prospective contributions to resolving the puzzle. In so doing, we hope to further consideration of how behavioral genetics findings may advance studies of social stratification beyond the effort to articulate specific genetic influences.

What about the behavioral constellation of advantage?

Many short-sighted behaviors are more common among poorer people. These behaviors are neither evolutionarily nor historically unusual and have strong contemporary encouragement. The bigger puzzle is their lower frequency among the affluent. The behaviors also have clear cultural and normative aspects that limit the usefulness of strictly individualist theories.