Genomic Architecture of Regional Measures of Cerebral Cortical Thickness Open Access

Abstract

The cerebral cortex can be organized into dimensions of brain regions with shared genetic influences on cortical thickness. Such dimensions represent novel cortical phenotypes that can facilitate future genomic investigation into diverse and complex behavioral traits. Understanding the underlying organizational principles of genetic influences on brain structure is a critical step towards a mechanistic model of how specific genes influence brain anatomy and possibly mediate neuropsychiatric risk. The current study models the structure of genetic correlations among regional measures of cortical thickness using Genomic Structural Equation Modeling (Genomic SEM), a recently developed R package that applies the methods of structural equation modeling to genetic covariances. Factor analyses identified eight genomic brain factors that do not conform to traditionally defined brain structure boundaries and relate to a combination of biological and structural principles instead. Such findings highlight the complexity of genetic influences on cortical morphology and set the stage for elucidating the micro and macrostructural bases of complex traits such as personality and psychopathology.

Table of Contents

Table of Contents

Genomic Architecture of Regional Measures of Cerebral Cortical Thickness ..................... 7

Genetic Correlations Between Brain Regions .......................................................... 9

The Current Study ................................................................................................... 14

Materials and Methods ........................................................................................................ 16

Summary Statistics: ENIGMA ................................................................................ 16

Quality Control Procedures ..................................................................................... 17

Linkage Disequilibrium Score Regression .............................................................. 18

Exploratory Factor Analyses ................................................................................... 20

Confirmatory Factor Analyses ................................................................................ 20

Results ................................................................................................................................. 23

Discussion ........................................................................................................................... 25

Characterization of Resulting Genomic Factors ..................................................... 26

Cortical Thickness, Psychopathology, and Personality .......................................... 29

Limitations ............................................................................................................... 32

Future Directions ..................................................................................................... 34

Conclusion: In Search of Mechanistic Understanding ............................................ 37

Tables .................................................................................................................................. 39

Figures ................................................................................................................................. 43

References ............................................................................................................................47

About this Master's Thesis

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School	Laney Graduate School
Department	Psychology
Subfield / Discipline	Clinical Psychology
Degree	M.A.
Submission	Master's Thesis
Language	English
Research Field	Psychology, Psychobiology Biology, Genetics Biology, Neuroscience
Keyword	psychology
Committee Chair / Thesis Advisor	Irwin Waldman, Emory University
Committee Members	Daniel Dilks, Emory University Michael Treadway, Emory University

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