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Structural Asymmetry in the Frontal and Temporal Lobes Is Associated with PCSK6 VNTR Polymorphism

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Abstract

The nodal cascade influences the development of bodily asymmetries in humans and other vertebrates. The gene PCSK6 has shown a regulatory function during left-right axis formation and is therefore thought to influence bodily left-right asymmetries. However, it is not clear if variation in this gene is also associated with structural asymmetries in the brain. We genotyped an intronic 33bp PCSK6 variable number tandem repeat (VNTR) polymorphism that has been associated with handedness in a cohort of healthy adults. We acquired T1-weighted structural MRI images of 320 participants and defined cortical surface and thickness for each HCP region. The results demonstrate a significant association between PCSK6 VNTR genotypes and gray matter asymmetry in the superior temporal sulcus, which is involved in voice perception. Heterozygous individuals who carry a short (≤ 6 repeats) and a long (≥ 9 repeats) PCSK6 VNTR allele show stronger rightward asymmetry. Further associations were evident in the dorsolateral prefrontal cortex. Here, individuals homozygous for short alleles show a more pronounced asymmetry. This shows that PCSK6, a gene that has been implicated in the ontogenesis of bodily asymmetries by regulating the nodal cascade, is also relevant for structural asymmetries in the human brain.

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Abbreviations

SNP:

single nucleotid polymorphism

VNTR:

variable number tandem repeat

PCR:

polymerase chain reaction

HCPMMP:

human connectome project’s multi-modal parcellation

LQ:

lateralization quotient

STSda:

superior temporal sulcus dorsal anterior

9-46d:

central portion of the dorsolateral prefrontal cortex

PT:

planum temporale

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Acknowledgments

The authors thank Katharina Berger for her support during the behavioral measurements. Further, the authors thank PHILIPS Germany (Burkhard Mädler) for the scientific support with the MRI measurements as well as Tobias Otto for the technical assistance.

Funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) grant number OC 127/9-1, GU 227/16-1, GE 2777/2-1, SFB 940 project B08, and SFB 1280 project A03 and the Mercur Foundation grant number An-2015-0044.

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Authors and Affiliations

  1. Institute of Cognitive Neuroscience, Biopsychology, Department of Psychology, Ruhr-University Bochum, Universitätsstraße 150, Room: IB 6/109, 44780, Bochum, Germany

    Gesa Berretz, Patrick Friedrich, Christoph Fraenz, Caroline Schlüter, Onur Güntürkün, Erhan Genç & Sebastian Ocklenburg

  2. Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany

    Larissa Arning, Wanda M. Gerding & Jörg T. Epplen

  3. Faculty of Health, ZBAF, University of Witten/Herdecke, Witten, Germany

    Jörg T. Epplen

  4. Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany

    Christian Beste

  5. Faculty of Psychology, School of Science, TU Dresden, Dresden, Germany

    Christian Beste

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  1. Gesa Berretz
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  2. Larissa Arning
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  3. Wanda M. Gerding
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  4. Patrick Friedrich
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  9. Christian Beste
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  10. Erhan Genç
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  11. Sebastian Ocklenburg
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Correspondence to Gesa Berretz.

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Berretz, G., Arning, L., Gerding, W.M. et al. Structural Asymmetry in the Frontal and Temporal Lobes Is Associated with PCSK6 VNTR Polymorphism. Mol Neurobiol 56, 7765–7773 (2019). https://doi.org/10.1007/s12035-019-01646-1

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