Biology subjects

Heeringa, S. G.

Publications and source records attributed to Heeringa, S. G..

3 recordsLinked to original sources

bioRxiv2020

Meaningful Effects in the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and childrens health in the United States. A cohort of n= 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

neuroscience↗

bioRxiv2020

A Guide for Population-based Analysis of the Adolescent Brain Cognitive Development (ABCD) Study Baseline Data

ABCD is a longitudinal, observational study of U.S. children, ages 9-10 at baseline, recruited at random from the household populations in defined catchment areas for each of 21 study sites. The 21 geographic locations that comprise the ABCD research sites are nationally distributed and generally represent the range of demographic and socio-economic diversity of the U.S. birth cohorts that comprise the ABCD study population. The clustering of participants and the potential for selection bias in study site selection and enrollment are features of the ABCD observational study design that are informative for statistical estimation and inference. Both multi-level modeling and robust survey design-based methods can be used to account for clustering of sampled ABCD children in the 21 study sites. Covariate controls in analytical models and propensity weighting methods that calibrate ABCD weighted distributions to nationally-representative controls from the American Community Survey (ACS) can be employed in analysis to account for known informative sample design features or to attenuate potential demographic and socio-economic selection bias in the national sampling and recruitment of eligible children. This guide will present results of an empirical investigation of the ABCD baseline data that compares the statistical efficiency of multi-level modeling and distribution-free design-based approaches--both weighted and unweighted--to analyses of the ABCD baseline data. Specific recommendations will be provided for researchers on robust, efficient approaches to both descriptive and multivariate analyses of the ABCD baseline data.

neuroscience↗

bioRxiv2019

Genomewide Analyses of Psychological Resilience in US Army Soldiers

Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genomewide association studies (GWAS) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from pre- to post-deployment) resilience among European (EUR) ancestry soldiers in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS). Self-assessed resilience (N=11,492) was found to have significant common-variant heritability (h2=0.162, se=0.050, p=5.37e-4), and to be significantly negatively genetically correlated with neuroticism (rg= -0.388, p=0.0092). GWAS results from the EUR soldiers revealed a genomewide significant locus (4 SNPs in LD; top SNP: rs4260523, p=5.654e-09) on an intergenic region on Chr 4 upstream from DCLK2 (Doublecortin-Like Kinase 2), a member of the doublecortin (DCX) family of kinases that promote survival and regeneration of injured neurons. A second gene, KLHL36 (Kelch Like Family Member 36) was detected at gene-wise genomewide significance (p=1.89e-06). A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very preliminary results, genomewide significant association with outcome-based resilience was found for one locus (top SNP: rs12580015) on Chr 12 downstream from SLC15A5 (solute carrier family 15 member 5) in the small group (N=581) of subjects exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stress-related psychopathology and potentially point to new avenues for therapeutic intervention.

genetics↗