Genetic and Environmental Variation in Continuous Phenotypes in the ABCD Study®.

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can serve as a reference point for future behavior genetic studies of this publicly available dataset. Data were analyzed from 772 pairs of twins aged 9-10 years at study inception, with zygosity determined using genotypic data, recruited and assessed at four twin hub sites. The online tool provides twin correlations and both standardized and unstandardized estimates of additive genetic, and environmental variation for 14,500 continuously distributed phenotypic features, including: structural and functional neuroimaging, neurocognition, personality, psychopathology, substance use propensity, physical, and environmental trait variables. The estimates were obtained using an unconstrained variance approach, so they can be incorporated directly into meta-analyses without upwardly biasing aggregate estimates. The results indicated broad consistency with prior literature where available and provided novel estimates for phenotypes without prior twin studies or those assessed at different ages. Effects of site, self-identified race/ethnicity, age and sex were statistically controlled. Results from genetic modeling of all 53,172 continuous variables, including 38,672 functional MRI variables, will be accessible via the user-friendly open-access web interface we have established, and will be updated as new data are released from the ABCD Study. This paper provides an overview of the initial results from the twin study embedded within the ABCD Study, an introduction to the primary research domains in the ABCD study and twin methodology, and an evaluation of the initial findings with a focus on data quality and suitability for future behavior genetic studies using the ABCD dataset. The broad introductory material is provided in recognition of the multidisciplinary appeal of the ABCD Study. While this paper focuses on univariate analyses, we emphasize the opportunities for multivariate, developmental and causal analyses, as well as those evaluating heterogeneity by key moderators such as sex, demographic factors and genetic background.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

Hierarchical genetic organization of human cortical surface area.

Surface area of the cerebral cortex is a highly heritable trait, yet little is known about genetic influences on regional cortical differentiation in humans. Using a data-driven, fuzzy clustering technique with magnetic resonance imaging data from 406 twins, we parceled cortical surface area into genetic subdivisions, creating a human brain atlas based solely on genetically informative data. Boundaries of the genetic divisions corresponded largely to meaningful structural and functional regions; however, the divisions represented previously undescribed phenotypes different from conventional (non-genetically based) parcellation systems. The genetic organization of cortical area was hierarchical, modular, and predominantly bilaterally symmetric across hemispheres. We also found that the results were consistent with human-specific regions being subdivisions of previously described, genetically based lobar regionalization patterns.

Older patients with schizophrenia: does military veteran status matter?

OBJECTIVE: : The objective of this study was to examine the influence of military veteran status within a data set of older patients with schizophrenia or schizoaffective disorder. METHODS: : The data set was examined to determine whether veteran status influenced psychopathology, quality of life, cognitive performance, and everyday functioning among 746 male participants. RESULTS: : There were no significant differences between the groups on measures of premorbid functioning or psychopathology. Veterans in the sample were older, had a higher likelihood of being married (or previously married), had a lower likelihood of living in a board-and-care facility, and had a later age of onset of schizophrenia compared with nonveterans. Though veterans reported worse physical health, they also had better everyday functioning and better performance on some cognitive tasks than nonveterans. Fewer veterans endorsed current use of substances than nonveterans. CONCLUSIONS: : There were several differences based on veteran status, including everyday functioning, health-related quality of life, cognitive performance, and current substance use.

Genetic influences on cortical regionalization in the human brain.

Animal data demonstrate that the development of distinct cortical areas is influenced by genes that exhibit highly regionalized expression patterns. In this paper, we show genetic patterning of cortical surface area derived from MRI data from 406 adult human twins. We mapped genetic correlations of areal expansion between selected seed regions and all other cortical locations, with the selection of seed points based on results from animal studies. "Marching seeds" and a data-driven, hypothesis-free, fuzzy-clustering approach provided convergent validation. The results reveal strong anterior-to-posterior graded, bilaterally symmetric patterns of regionalization, largely consistent with patterns previously reported in nonhuman mammalian models. Broad similarities in genetic patterning between rodents and humans might suggest a conservation of cortical patterning mechanisms, whereas dissimilarities might reflect the functionalities most essential to each species.

Racial and ethnic service use disparities among homeless adults with severe mental illnesses receiving ACT.

OBJECTIVE: Case management-based interventions aimed at improving quality of care have the potential to narrow racial and ethnic disparities among people with chronic illnesses. The aim of this study was to assess the equity effects of assertive community treatment (ACT), an evidence-based case management intervention, among homeless adults with severe mental illness. METHODS: This study used baseline, three-, and 12-month data for 6,829 black, Latino, and white adults who received ACT services through the ACCESS study (Access to Community Care and Effective Services and Support). Zero-inflated Poisson random regression models were used to estimate the adjusted probability of use of outpatient psychiatric services and, among service users, the intensity of use. Odds ratios and rate ratios (RRs) were computed to assess disparities at baseline and over time. RESULTS: No disparities were found in probability of use at baseline or over time. Compared with white users, baseline intensity of use was lower for black users (RR=.89; 95% confidence interval [CI]=.83-.96) and Latino users (RR=.65; CI=.52-.81]). Intensity did not change over time for whites, but it did for black and Latino users. Intensity increased for blacks between baseline and three months (RR=1.11, CI=1.06-1.17]) and baseline and 12 months (RR=1.17, CI=1.11-1.22]). Intensity of use dropped for Latinos between baseline and three months (RR=.83, CI=.70-.98). CONCLUSIONS: Receipt of ACT was associated with a reduction in service use disparities for blacks but not for Latinos. Findings suggest that ACT's equity effects differ depending on race-ethnicity.

Assessing quality of diabetes care by measuring longitudinal changes in hemoglobin A1c in the Veterans Health Administration.

CONTEXT: A1c levels are widely used to assess quality of diabetes care provided by health care systems. Currently, cross-sectional measures are commonly used for such assessments. OBJECTIVE: To study within-patient longitudinal changes in A1c levels at Veterans Health Administration (VHA) facilities as an alternative to cross-sectional measures of quality of diabetes care. DESIGN: Longitudinal study using institutional data on individual patient A1c level over time (October 1, 1998-September 30, 2000) with time variant and invariant covariates. SETTING: One hundred and twenty-five VHA facilities nationwide, October 1, 1998-September 30, 2000. PATIENTS: Diabetic veteran users with A1c measurement performed using National Glycosylated Hemoglobin Standardization Project certified A1c lab assay methods. EXPOSURES: Characteristics unlikely to reflect quality of care, but known to influence A1c levels, demographics, and baseline illness severity. MAIN OUTCOME MEASURE: Monthly change in A1c for average patient cared for at each facility. RESULTS: The preponderance of facilities showed monthly declines in within-patient A1c over the study period (mean change of -0.0148 A1c units per month, range -0.074 to 0.042). Individual facilities varied in their monthly change, with 105 facilities showing monthly declines (70 significant at .05 level) and 20 showing monthly increases (5 significant at .05 level). Case-mix adjustment resulted in modest changes (mean change of -0.0131 case-mix adjusted A1c units per month, range -0.079 to 0.043). Facilities were ranked from worst to best, with attached 90 percent confidence intervals. Among the bottom 10 ranked facilities, four remained within the bottom decile with 90 percent confidence. CONCLUSIONS: There is substantial variation in facility-level longitudinal changes in A1c levels. We propose that evaluation of change in A1c levels over time can be used as a new measure to reflect quality of care provided to populations of individuals with chronic disease.