Quantifying the Polygenic Architecture of the Human Cerebral Cortex: Extensive Genetic Overlap between Cortical Thickness and Surface Area. (2nd June 2020)

• Record Type: Journal Article
• Authors: van der Meer, Dennis; Frei, Oleksandr; Kaufmann, Tobias; Chen, Chi-Hua; Thompson, Wesley K; O'Connell, Kevin S; Monereo Sánchez, Jennifer; Linden, David E J; Westlye, Lars T; Dale, Anders M; Andreassen, Ole A
• Is Part Of: Cerebral cortex. Volume 30:Number 10(2020)
• Page Start: 5597
• Page End: 5603
• Publication Date: 2020-06-02
• Subjects: cortical thickness -- parcellation -- pleiotropy -- polygenicity -- surface area; Cerebral cortex -- Periodicals; Brain -- Periodicals; 612.825
• DOI: 10.1093/cercor/bhaa146
• Languages: English
• ISSNs: 1047-3211

Abstract

Abstract: The thickness of the cerebral cortical sheet and its surface area are highly heritable traits thought to have largely distinct polygenic architectures. Despite large-scale efforts, the majority of their genetic determinants remain unknown. Our ability to identify causal genetic variants can be improved by employing brain measures that better map onto the biology we seek to understand. Such measures may have fewer variants but with larger effects, that is, lower polygenicity and higher discoverability. Using Gaussian mixture modeling, we estimated the number of causal variants shared between mean cortical thickness and total surface area, as well as the polygenicity and discoverability of regional measures. We made use of UK Biobank data from 30 880 healthy White European individuals (mean age 64.3, standard deviation 7.5, 52.1% female). We found large genetic overlap between total surface area and mean thickness, sharing 4016 out of 7941 causal variants. Regional surface area was more discoverable ( P = 2.6 × 10 −6 ) and less polygenic ( P = 0.004) than regional thickness measures. These findings may serve as a roadmap for improved future GWAS studies; knowledge of which measures are most discoverable may be used to boost identification of genetic predictors and thereby gain a better understanding of brain morphology.