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Article

Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population

by
Kevin Kirchner
1,
Linda Garvert
1,
Katharina Wittfeld
1,2,
Sabine Ameling
3,4,
Robin Bülow
5,
Henriette Meyer zu Schwabedissen
6,
Matthias Nauck
4,7,
Henry Völzke
4,8,
Hans J. Grabe
1,2 and
Sandra Van der Auwera
1,2,*
1
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany
2
German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, 17475 Greifswald, Germany
3
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany
4
German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany
5
Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17475 Greifswald, Germany
6
Department Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland
7
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, Germany
8
Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(2), 1120; https://doi.org/10.3390/ijms24021120
Submission received: 19 December 2022 / Revised: 2 January 2023 / Accepted: 3 January 2023 / Published: 6 January 2023
(This article belongs to the Special Issue Molecular Research on Depression)
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Abstract

The aim of this study was to disentangle the effects of various genetic factors on hippocampal subfield volumes using three different approaches: a biologically driven candidate gene approach, a hypothesis-free GWAS approach, and a polygenic approach, where AD risk alleles are combined with a polygenic risk score (PRS). The impact of these genetic factors was investigated in a large dementia-free general population cohort from the Study of Health in Pomerania (SHIP, n = 1806). Analyses were performed using linear regression models adjusted for biological and environmental risk factors. Hippocampus subfield volume alterations were found for APOE ε4, BDNF Val, and 5-HTTLPR L allele carriers. In addition, we were able to replicate GWAS findings, especially for rs17178139 (MSRB3), rs1861979 (DPP4), rs7873551 (ASTN2), and rs572246240 (MAST4). Interaction analyses between the significant SNPs as well as the PRS for AD revealed no significant results. Our results confirm that hippocampal volume reductions are influenced by genetic variation, and that different variants reveal different association patterns that can be linked to biological processes in neurodegeneration. Thus, this study underlines the importance of specific genetic analyses in the quest for acquiring deeper insights into the biology of hippocampal volume loss, memory impairment, depression, and neurodegenerative diseases.
Keywords: hippocampal subfields; verbal memory; APOE; BDNF; 5-HTTLPR; polygenic score; general population; trisynaptic circuit; candidate genes; depression hippocampal subfields; verbal memory; APOE; BDNF; 5-HTTLPR; polygenic score; general population; trisynaptic circuit; candidate genes; depression

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MDPI and ACS Style

Kirchner, K.; Garvert, L.; Wittfeld, K.; Ameling, S.; Bülow, R.; Meyer zu Schwabedissen, H.; Nauck, M.; Völzke, H.; Grabe, H.J.; Van der Auwera, S. Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population. Int. J. Mol. Sci. 2023, 24, 1120. https://doi.org/10.3390/ijms24021120

AMA Style

Kirchner K, Garvert L, Wittfeld K, Ameling S, Bülow R, Meyer zu Schwabedissen H, Nauck M, Völzke H, Grabe HJ, Van der Auwera S. Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population. International Journal of Molecular Sciences. 2023; 24(2):1120. https://doi.org/10.3390/ijms24021120

Chicago/Turabian Style

Kirchner, Kevin, Linda Garvert, Katharina Wittfeld, Sabine Ameling, Robin Bülow, Henriette Meyer zu Schwabedissen, Matthias Nauck, Henry Völzke, Hans J. Grabe, and Sandra Van der Auwera. 2023. "Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population" International Journal of Molecular Sciences 24, no. 2: 1120. https://doi.org/10.3390/ijms24021120

APA Style

Kirchner, K., Garvert, L., Wittfeld, K., Ameling, S., Bülow, R., Meyer zu Schwabedissen, H., Nauck, M., Völzke, H., Grabe, H. J., & Van der Auwera, S. (2023). Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population. International Journal of Molecular Sciences, 24(2), 1120. https://doi.org/10.3390/ijms24021120

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