31 Jan Polygenic Risk Scores Linked to Intelligence, ADHD and Brain Findings
MedicalResearch.com Interview with:
Silvia Alemany, PhD first author
Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa”.
In collaboration with co-authors:
Philip Jansen,MD, MSc and
Tonya White, MD, PhD
Erasmus University Medical Center, Rotterdam
MedicalResearch.com: What is the background for this study?
Response: Individuals affected by psychiatric disorders can demonstrate morphological brain abnormalities when compared to healthy controls. Although both genetic and environmental factors can account for these brain abnormalities, we expect that genetic susceptibility for psychiatric disorders has the greatest influence on the development of the brain.
Genetic susceptibility for psychiatric disorders can be estimated at the individual level by generating polygenic risk scores. Using this methodology, genetic susceptibility to psychiatric disorders and cognition has been associated with behavior problems in childhood. These findings suggest that heritable neurobiological mechanisms are at play in very early in the course of the illnesses.
MedicalResearch.com: What are the main findings?
Response: In this study we sought to examine whether genetic susceptibility for psychiatric disorders and cognition, including intelligence and educational attainment, indexed using polygenic risk scores, influences brain morphology during childhood. The psychiatric disorders examined included schizophrenia, bipolar disorder, major depression disorder, autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). Additionally, we tested whether differences in brain morphology mediated associations between polygenic risk scores for psychiatric disorders and related behavioral phenotypes.
MedicalResearch.com: What should readers take away from your report?
Response: Our findings indicate that the neurobiological manifestation of polygenic susceptibility for ADHD, intelligence, and education involves early morphological differences in caudate and total brain volume during development. More specifically, genetic variants related to intelligence and education are positively associated with larger total brain volumes in children. However, genetic variants associated with ADHD were related to smaller caudate volume, a subcortical region of the brain that has been consistently found to be reduced in individuals affected by this disorder. Further analyses suggested that the reduction in caudate volume is mediating the association between polygenic risk for ADHD and the phenotypic expression of this disorder, but only among boys.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
- First, we recommend that future studies examining the effects of polygenic risk for ADHD consider the role of sex, since our findings suggest that genetic risk for ADHD may act differently in boys and girls.
- Second, polygenic risk related to schizophrenia showed no associations with brain morphological variation, however, behavioral effects of polygenic risk for schizophrenia were previously observed in the study sample. These findings must have neural correlates that we were unable to detect. Future studies in this or other pediatric samples may consider examining other neuroimaging phenotypes for example, brain function.
- Third, longitudinal neuroimaging studies are needed to examine whether polygenic risk for psychiatric disorders and cognition contribute to changes in developmental trajectories which would suggest a role in neural plasticity.
- Finally, how genetic variants related to psychopathology and cognition ultimately contribute to the development of the disease or trait may be also studied by incorporating environmental factors and examining their potential modifying or mediating roles.
Silvia Alemany, Philip R. Jansen, Ryan L. Muetzel, Natália Marques, Hanan El Marroun, Vincent W.V. Jaddoe, Tinca J.C. Polderman, Henning Tiemeier, Danielle Posthuma, Tonya White. Common Polygenic Variations for Psychiatric Disorders and Cognition in Relation to Brain Morphology in the General Pediatric Population. Journal of the American Academy of Child & Adolescent Psychiatry, 2019; DOI: 10.1016/j.jaac.2018.09.443
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