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Systems genomics analysis of complex cognitive traits

Freytag, Virginie. Systems genomics analysis of complex cognitive traits. 2017, Doctoral Thesis, University of Basel, Faculty of Psychology.

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Official URL: http://edoc.unibas.ch/diss/DissB_12287

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Abstract

The study of the genetic underpinnings of human cognitive traits is deemed an important tool to increase our understanding of molecular processes related to physiological and pathological cognitive functioning. The polygenic architecture of such complex traits implies that multiple naturally occurring genetic variations, each of small effect size, are likely to influence jointly the biological processes underlying cognitive ability. Genetic association results are yet devoid of biological context, thus limiting both the identification and functional interpretation of susceptibility variants. This biological gap can be reduced by the integrative analysis of intermediate molecular traits, as mediators of genomic action. In this thesis, I present results from two such systems genomics analyses, as attempts to identify molecular patterns underlying cognitive trait variability. In the first study, we adopted a system-level approach to investigate the relationship between global age-related patterns of epigenetic variation and cortical thickness, a brain morphometric measure that is linked to cognitive functioning. The integration of both genome-wide methylomic and genetic profiles allowed the identification of a peripheral molecular signature that showed association with both cortical thickness and episodic memory performance. In the second study, we explicitly modeled the interdependencies between local genetic markers and peripherally measured epigenetic variations. We thus generated robust estimators of epigenetic regulation and showed that these estimators resulted in the identification of epigenetic underpinnings of schizophrenia, a common genetically complex disorder. These results underscore the potential of systems genomics approaches, capitalizing on the integration of high-dimensional multi-layered molecular data, for the study of brain- related complex traits.
Advisors:Papassotiropoulos, Andreas and de Quervain, Dominique J.-F.
Faculties and Departments:07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:Freytag, Virginie and Papassotiropoulos, Andreas and de Quervain, Dominique J.-F.
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12287
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (102 Blätter)
Language:English
Identification Number:
Last Modified:30 May 2018 04:30
Deposited On:28 May 2018 12:45

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