Genetics of brain structure: Contributions from the vietnam era twin study of aging

Abstract

Understanding the genetics of neuropsychiatric disorders requires an understanding of the genetics of brain structure and function. The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study focused on cognitive and brain aging. Here, we describe basic science work carried out within the VETSA MRI study that provides meaningful contributions toward the study of neuropsychiatric disorders. VETSA produced the first comprehensive assessment of the heritability of cortical and subcortical brain structure sizes, all within the same individuals. We showed that neocortical thickness and surface area are largely genetically distinct. With continuous neocortical thickness maps, we demonstrated regional specificity of genetic influences, and that genetic factors did not conform to traditional regions of interest (ROIs). However, there was some evidence for different genetic factors accounting for different types of cortex, and for genetic relationships across cortical regions corresponding to anatomical and functional connectivity and brain maturation patterns. With continuous neocortical surface area maps, we confirmed the anterior–posterior gradient of genetic influences on cortical area patterning demonstrated in animal models. Finally, we used twin methods to create the first map of cortical ROIs based entirely on genetically informative data. We conclude that these genetically based cortical phenotypes may be more appropriate for genetic studies than traditional ROIs based on structure or function. Our results also suggest that cortical volume—the product of thickness and surface area is a problematic phenotype for genetic studies because two independent sets of genes may be obscured. Examples supporting the validity of these conclusions are provided.

Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality

“…Participants were 486 individuals with analyzable MRI and personality data who are part of a larger sample of 1237 twins who participated in wave 1 of the Vietnam Era Twin Study of Aging (VETSA: Kremen et al, 2013). Institutional Review Board approval was obtained at all sites.…”

Development of the Cerebral Cortex across Adolescence: A Multisample Study of Inter-Related Longitudinal Changes in Cortical Volume, Surface Area, and Thickness

“…Cortical volume is determined by surface area and thickness, and these components are influenced by different evolutionary (Geschwind and Rakic, 2013), genetic (Chen et al, 2013; Kremen et al, 2013), and cellular (Chenn and Walsh, 2002) processes, and show unique changes across different stages of life (Brown et al, 2012; Storsve et al, 2014; Wierenga et al, 2014; Lyall et al, 2015; Amlien et al, 2016). Knowledge about the relative contributions of surface area and thickness to developmental cortical volume changes, and the relationship between changes in surface area and thickness during adolescence, may provide important, although indirect, clues for understanding the biological processes underlying development of cortical structure.…”

Gene-Environment Interplay in Interpersonal Relationships across the Lifespan

“…We also now recognize that there electrical and biochemical "wiring" of the human brain to be connected with other people, and that social connectness plays a role in shaping the brain and later development (Hari and Kujala 2009;Insel 2010;Meyer-Lindenberg et al 2011;Van Overwall et al 2014). It is also evident that many brain structures are highly heritable (Kremen et al 2013). Conducting such research in the context of genetically informative designs could offer insight into the behavioral genetics of neural pathways involved in the development and maintenance of longterm attachments necessary to interpersonal relationships in older adult life.…”