Imaging local genetic influences on cortical folding

Aaron F. Alexander-Bloch, Armin Raznahan, Simon N. Vandekar, Jakob Seidlitz, Zhixin Lu, Samuel R. Matthias, Emma Knowles, Josephine Mollon, Amanda Rodrigue, Joanne E. Curran, Harald H.H. Görring, Theodore D. Satterthwaite, Raquel E. Gur, Danielle S. Bassett, Gil D. Hoftman, Godfrey Pearlson, Russell T. Shinohara, Siyuan Liu, Peter T. Fox, Laura AlmasyrJohn Blangero, David C. Glahn

Research output: Contribution to journalArticle

Abstract

Recent progress in deciphering mechanisms of human brain cortical folding leave unexplained whether spatially patterned genetic influences contribute to this folding. High-resolution in vivo brain MRI can be used to estimate genetic correlations (covariability due to shared genetic factors) in interregional cortical thickness, and biomechanical studies predict an influence of cortical thickness on folding patterns. However, progress has been hampered because shared genetic influences related to folding patterns likely operate at a scale that is much more local (<1 cm) than that addressed in prior imaging studies. Here, we develop methodological approaches to examine local genetic influences on cortical thickness and apply these methods to two large, independent samples. We find that such influences are markedly heterogeneous in strength, and in some cortical areas are notably stronger in specific orientations relative to gyri or sulci. The overall, phenotypic local correlation has a significant basis in shared genetic factors and is highly symmetric between left and right cortical hemispheres. Furthermore, the degree of local cortical folding relates systematically with the strength of local correlations, which tends to be higher in gyral crests and lower in sulcal fundi. The relationship between folding and local correlations is stronger in primary sensorimotor areas and weaker in association areas such as prefrontal cortex, consistent with reduced genetic constraints on the structural topology of association cortex. Collectively, our results suggest that patterned genetic influences on cortical thickness, measurable at the scale of in vivo MRI, may be a causal factor in the development of cortical folding.

Original languageEnglish (US)
Pages (from-to)7430-7436
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number13
DOIs
StatePublished - Mar 31 2020

Keywords

  • Cerebral cortex
  • Cortical folding
  • Cortical thickness
  • Genetic correlation
  • Structural MRI

ASJC Scopus subject areas

  • General

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  • Cite this

    Alexander-Bloch, A. F., Raznahan, A., Vandekar, S. N., Seidlitz, J., Lu, Z., Matthias, S. R., Knowles, E., Mollon, J., Rodrigue, A., Curran, J. E., Görring, H. H. H., Satterthwaite, T. D., Gur, R. E., Bassett, D. S., Hoftman, G. D., Pearlson, G., Shinohara, R. T., Liu, S., Fox, P. T., ... Glahn, D. C. (2020). Imaging local genetic influences on cortical folding. Proceedings of the National Academy of Sciences of the United States of America, 117(13), 7430-7436. https://doi.org/10.1073/pnas.1912064117