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Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes

van der Meer, Dennis and Rokicki, Jaroslav and Kaufmann, Tobias and Córdova-Palomera, Aldo and Moberget, Torgeir and Alnæs, Dag and Bettella, Francesco and Frei, Oleksandr and Doan, Nhat Trung and Sønderby, Ida E. and Smeland, Olav B. and Agartz, Ingrid and Bertolino, Alessandro and Bralten, Janita and Brandt, Christine L. and Buitelaar, Jan K. and Djurovic, Srdjan and van Donkelaar, Marjolein and Dørum, Erlend S. and Espeseth, Thomas and Faraone, Stephen V. and Fernández, Guillén and Fisher, Simon E. and Franke, Barbara and Haatveit, Beathe and Hartman, Catharina A. and Hoekstra, Pieter J. and Håberg, Asta K. and Jönsson, Erik G. and Kolskår, Knut K. and Le Hellard, Stephanie and Lund, Martina J. and Lundervold, Astri J. and Lundervold, Arvid and Melle, Ingrid and Monereo Sánchez, Jennifer and Norbom, Linn C. and Nordvik, Jan E. and Nyberg, Lars and Oosterlaan, Jaap and Papalino, Marco and Papassotiropoulos, Andreas and Pergola, Giulio and de Quervain, Dominique J. F. and Richard, Geneviève and Sanders, Anne-Marthe and Selvaggi, Pierluigi and Shumskaya, Elena and Steen, Vidar M. and Tønnesen, Siren and Ulrichsen, Kristine M. and Zwiers, Marcel P. and Andreassen, Ole A. and Westlye, Lars T. and Alzheimer's Disease Neuroimaging Initiative, and Pediatric Imaging, Neurocognition and Genetics Study, . (2018) Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes. Molecular Psychiatry. pp. 1-13.

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Official URL: https://edoc.unibas.ch/66832/

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Abstract

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10; -16; ) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:Papassotiropoulos, Andreas
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:1359-4184
e-ISSN:1476-5578
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:26 Nov 2018 14:00
Deposited On:26 Nov 2018 14:00

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