Replication of a hippocampus specific effect of the tescalcin regulating variant rs7294919 on gray matter structure

Janik Goltermann; Nils Opel; Ronny Redlich; Jonathan Repple; Claas Kaehler; Dominik Grotegerd; Katharina Dohm; Elisabeth J Leehr; Joscha Böhnlein; Katharina Förster; Susanne Meinert; Verena Enneking; Daniel Emden; Ramona Leenings; Nils R Winter; Tim Hahn; Sami Mikhail; Andreas Jansen; Axel Krug; Igor Nenadić; Marcella Rietschel; Stephanie H Witt; Stefanie Heilmann-Heimbach; Per Hoffmann; Andreas J Forstner; Markus M Nöthen; Bernhard T Baune; Tilo Kircher; Udo Dannlowski

doi:10.1016/j.euroneuro.2020.03.021

Replication of a hippocampus specific effect of the tescalcin regulating variant rs7294919 on gray matter structure

Eur Neuropsychopharmacol. 2020 Jul:36:10-17. doi: 10.1016/j.euroneuro.2020.03.021. Epub 2020 May 23.

Authors

Janik Goltermann¹, Nils Opel², Ronny Redlich¹, Jonathan Repple¹, Claas Kaehler³, Dominik Grotegerd¹, Katharina Dohm¹, Elisabeth J Leehr¹, Joscha Böhnlein¹, Katharina Förster¹, Susanne Meinert¹, Verena Enneking¹, Daniel Emden¹, Ramona Leenings¹, Nils R Winter¹, Tim Hahn¹, Sami Mikhail¹, Andreas Jansen⁴, Axel Krug⁴, Igor Nenadić⁴, Marcella Rietschel⁵, Stephanie H Witt⁵, Stefanie Heilmann-Heimbach⁶, Per Hoffmann⁷, Andreas J Forstner⁸, Markus M Nöthen⁶, Bernhard T Baune⁹, Tilo Kircher⁴, Udo Dannlowski¹⁰

Affiliations

¹ Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany.
² Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany; Interdisciplinary Centre for Clinical Research (IZKF), University of Mü̈nster, Münster, Germany.
³ Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany; Department of Mathematics and Computer Science, University of Münster, Germany.
⁴ Department of Psychiatry, University of Marburg, Germany.
⁵ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁶ Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
⁷ Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland.
⁸ Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland; Centre for Human Genetics, University of Marburg, Marburg, Germany; Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
⁹ Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany; Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
¹⁰ Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, Building A9, 48149 Münster, Germany. Electronic address: udo.dannlowski@uni-muenster.de.

PMID: 32451266
DOI: 10.1016/j.euroneuro.2020.03.021

Abstract

While the hippocampus remains a region of high interest for neuropsychiatric research, the precise contributors to hippocampal morphometry are still not well understood. We and others previously reported a hippocampus specific effect of a tescalcin gene (TESC) regulating single nucleotide polymorphism (rs7294919) on gray matter volume. Here we aimed to replicate and extend these findings. Two complementary morphometric approaches (voxel based morphometry (VBM) and automated volumetric segmentation) were applied in a well-powered cohort from the Marburg-Münster Affective Disorder Cohort Study (MACS) including N=1137 participants (n=636 healthy controls, n=501 depressed patients). rs7294919 homozygous T-allele genotype was significantly associated with lower hippocampal gray matter density as well as with reduced hippocampal volume. Exploratory whole brain VBM analyses revealed no further associations with gray matter volume outside the hippocampus. No interaction effects of rs7294919 with depression nor with childhood trauma on hippocampal morphometry could be detected. Hippocampal subfield analyses revealed similar effects of rs7294919 in all hippocampal subfields. In sum, our results replicate a hippocampus specific effect of rs7294919 on brain structure. Due to the robust evidence for a pronounced association between the reported polymorphism and hippocampal morphometry, future research should consider investigating the potential clinical and functional relevance of the reported association.

Keywords: Depression; Genetics; Hippocampus; MRI; Tescalcin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Calcium-Binding Proteins / genetics*
Cohort Studies
Cross-Sectional Studies
Depressive Disorder, Major / diagnostic imaging
Depressive Disorder, Major / genetics
Female
Genetic Variation / genetics*
Gray Matter / diagnostic imaging*
Hippocampus / diagnostic imaging*
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics*
Young Adult

Substances

Calcium-Binding Proteins
TESC protein, human