Externalizing disorders are highly heritable psychiatric conditions that typically present in childhood or
adolescence and co-occur within individuals. Recent genome-wide association studies have successfully
identified hundreds of genetic loci linked to externalizing disorders – many of which are known to be involved
in neurodevelopment. Bioinformatic results have bolstered this connection, revealing that the shared genetic
architecture of externalizing is enriched for genes that are preferentially expressed during the prenatal period.
However, despite these important advances, our understanding of the precise neurodevelopmental
mechanisms involved remains limited. Identifying the specific processes that augment the risk for and
development of externalizing psychopathology would greatly advance translational knowledge in this domain.
In this application, Dr. Travis Mallard will investigate the central hypothesis that externalizing psychopathology
is influenced by genes involved in critical neurodevelopmental programs that partially exert their influence via
subtle-but-deleterious effects on cortical structure. Specifically, Dr. Mallard will use the Genomic Structural
Equation Modeling framework to advance genetic discovery for externalizing disorders (Aim 1), and elucidate
the genetic relationships between externalizing and brain structure across development (Aim 2). Using cutting-
edge informatic methods, he will then characterize the multidimensional functional profiles of risk genes (Aim
3). These studies will use existing large-scale neurogenomic and clinical datasets and advanced statistical
methods that the applicant and his mentorship team have pioneered. Together, these aims will help clarify the
complex molecular underpinnings and developmental neurogenomic pathways in externalizing disorders.
With his unique background in clinical psychology, complex trait genetics, and human neuroscience, Dr.
Mallard is well-qualified to execute the proposed research and training objectives. The four-year training
program will foster the applicant’s technical skillset, professional development, and progression toward
independence, and the proposed studies will generate vital preliminary data for a future R01 application with
therapeutic potential. Dr. Mallard will continue his mentee relationships with Drs. Jordan Smoller and Tian Ge,
while receiving training and mentorship in functional genomics and transcriptomics from Dr. Michael Gandal.
He has also enlisted several additional renowned clinical scientists to serve on his Expert Advisory Committee:
Dr. Danielle Dick, an expert in the genetic etiology of externalizing disorders; Dr. Elliot Tucker-Drob, a
statistical genetics and cognitive development expert; and Dr. Armin Raznahan, an expert in developmental
neuroscience and genomics. The collaborative research environment is ideal for furthering Dr. Mallard’s goal
of becoming an independent clinician-scientist in psychiatric genetics.