UW Gene-Environment Study
The primary purpose of the study is to examine how neurobiological (i.e., temperament, genetics) and environmental factors independently and jointly influence variation in early childhood self-control and reward sensitivity, two key constructs within the NIMH Research Domains Criteria (RDoC). Self-control and reward sensitivity are highly heritable, multifactorial constructs with cross-cutting associations to the externalizing disorders, such as oppositional defiant disorder, conduct disorder, and attention-deficit/hyperactivity disorder. Yet, not all children with deficiencies in these traits develop externalizing problems. The current study utilizes a developmental psychopathology framework to examine the neurobiological and environmental factors that underlie these traits, and to determine how variation across these factors may uniquely “set the stage” for behavioral development
Add Health Study
Our project uses data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) (http://www.cpc.unc.edu/projects/addhealth) to investigate the independent and interactive roles of genes and environments on antisocial behavior trajectories, from adolescence to adulthood. Our specific aim is to test the theory that certain genes will interact not only with negative environmental risk factors, but also with enriched/positive environmental factors (i.e., neighborhood characteristics, religiosity, social support, relationships with parents) to predict individual variation in antisocial behavior trajectories.
Key collaborators: Ashley Wazana, MD, Alexia Jolicoeur-Martineau, Ezster Szekely, (McGill University); Jonathan Martinez, Ph.D. (California State University-Northridge); Qiongshi Lu, Ph.D., Bowen Hu
Wisconsin Longitudinal Study (WLS)
The Wisconsin Longitudinal Study (WLS) is a long-term study of a random sample of 10,317 men and women who graduated from Wisconsin high schools in 1957. The WLS provides an opportunity to study the life course, intergenerational transfers and relationships, family functioning, physical and mental health and well-being, and morbidity and mortality from late adolescence through 2011. WLS data also cover social background, youthful aspirations, schooling, military service, labor market experiences, family characteristics and events, social participation, psychological characteristics and retirement. We are currently using genetic information from WLS participants to test the role of genetic factors underlying neuroticism and their interactive effects with social support/stress on health and behavioral outcomes in older adults. The goal of this study is to test differential susceptibility theory by interrogating both dimensions of social impact (support and stress) on health and behavioral outcomes as they relate to neuroticism. For more information about WLS: https://www.ssc.wisc.edu/wlsresearch/
Key collaborators: Jan Greenberg, Ph.D., Jinkuk Hong, Ph.D., Qiongshi Lu, Ph.D., Marsha Mailick, Ph.D.
Neurogenetics of ADHD Study
Attention-deficit/hyperactivity disorder (ADHD) is a heritable, neurodevelopmental disorder with a high prevalence in the population, affecting between 8-12% of children and adolescents worldwide. Genetic influences account for nearly 80% of its overall etiology, yet its precise genetic architecture remains poorly characterized. The ascendency of genome-wide association studies (GWAS) for ADHD have led to new discoveries with respect to the genes involved in its pathogenesis, but these studies provide no direct evidence about gene function, including its effect on the brain and subsequent behavior. Linking genome-wide signals with neural function is crucial for understanding the biological mechanisms of risk for ADHD and may lead to novel targets for intervention. This study integrates genomics, bioinformatics data and neuroimaging techniques to precisely characterize the brain mechanisms underlying genome-wide risk for ADHD.
Key collaborators: Ryan Herringa, M.D., Ph.D., Qiongshi Lu, Ph.D.
Genetics of a General Factor in Psychopathology Study
Psychiatric disorders tend to co-occur. This phenomenon (i.e., “comorbidity”) is a hallmark of the Diagnostic and Statistical Manual of Mental Disorders and an especially major issue in the emerging field of psychiatric genetics, since it greatly complicates our search for specific genes for specific disorders. There is increasing evidence that psychopathology may have a hierarchical rather than categorical taxonomy, such that a single major source of risk may be shared across all of the disorders and that other risk factors may contribute to the development of each specific disorder. This study uses individual genotype and phenotype data from the Neurodevelopmental Genomics: Trajectories of Complex Phenotypes (i.e., PNC) dataset to characterize the genetic variation underlying the general risk for psychopathology (i.e., the general factor) and specific risk for each disorder (specific factors).
Key collaborators: Qiongshi Lu, Ph.D.