Bibliographic Details
| Title: |
Genetic factors influencing a neurobiological substrate for psychiatric disorders |
| Authors: |
Till F. M. Andlauer, Thomas W. Mühleisen, Felix Hoffstaedter, Alexander Teumer, Katharina Wittfeld, Anja Teuber, Céline S. Reinbold, Dominik Grotegerd, Robin Bülow, Svenja Caspers, Udo Dannlowski, Stefan Herms, Per Hoffmann, Tilo Kircher, Heike Minnerup, Susanne Moebus, Igor Nenadić, Henning Teismann, Uwe Völker, Amit Etkin, Klaus Berger, Hans J. Grabe, Markus M. Nöthen, Katrin Amunts, Simon B. Eickhoff, Philipp G. Sämann, Bertram Müller-Myhsok, Sven Cichon |
| Source: |
Translational Psychiatry, Vol 11, Iss 1, Pp 1-13 (2021) |
| Publisher Information: |
Nature Publishing Group, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
| Subject Terms: |
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| More Details: |
Abstract A retrospective meta-analysis of magnetic resonance imaging voxel-based morphometry studies proposed that reduced gray matter volumes in the dorsal anterior cingulate and the left and right anterior insular cortex—areas that constitute hub nodes of the salience network—represent a common substrate for major psychiatric disorders. Here, we investigated the hypothesis that the common substrate serves as an intermediate phenotype to detect genetic risk variants relevant for psychiatric disease. To this end, after a data reduction step, we conducted genome-wide association studies of a combined common substrate measure in four population-based cohorts (n = 2271), followed by meta-analysis and replication in a fifth cohort (n = 865). After correction for covariates, the heritability of the common substrate was estimated at 0.50 (standard error 0.18). The top single-nucleotide polymorphism (SNP) rs17076061 was associated with the common substrate at genome-wide significance and replicated, explaining 1.2% of the common substrate variance. This SNP mapped to a locus on chromosome 5q35.2 harboring genes involved in neuronal development and regeneration. In follow-up analyses, rs17076061 was not robustly associated with psychiatric disease, and no overlap was found between the broader genetic architecture of the common substrate and genetic risk for major depressive disorder, bipolar disorder, or schizophrenia. In conclusion, our study identified that common genetic variation indeed influences the common substrate, but that these variants do not directly translate to increased disease risk. Future studies should investigate gene-by-environment interactions and employ functional imaging to understand how salience network structure translates to psychiatric disorder risk. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2158-3188 |
| Relation: |
https://doaj.org/toc/2158-3188 |
| DOI: |
10.1038/s41398-021-01317-7 |
| Access URL: |
https://doaj.org/article/8ed5970b609a44bdbe4d70c1a628c65c |
| Accession Number: |
edsdoj.8ed5970b609a44bdbe4d70c1a628c65c |
| Database: |
Directory of Open Access Journals |
