Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes
-
Published:2018-10-02
Issue:11
Volume:25
Page:3053-3065
-
ISSN:1359-4184
-
Container-title:Molecular Psychiatry
-
language:en
-
Short-container-title:Mol Psychiatry
Author:
van der Meer DennisORCID, , Rokicki Jaroslav, Kaufmann Tobias, Córdova-Palomera Aldo, Moberget TorgeirORCID, Alnæs DagORCID, Bettella FrancescoORCID, Frei Oleksandr, Doan Nhat Trung, Sønderby Ida E., Smeland Olav B., Agartz Ingrid, Bertolino Alessandro, Bralten Janita, Brandt Christine L., Buitelaar Jan K., Djurovic SrdjanORCID, van Donkelaar MarjoleinORCID, Dørum Erlend S., Espeseth Thomas, Faraone Stephen V.ORCID, Fernández Guillén, Fisher Simon E.ORCID, Franke BarbaraORCID, Haatveit Beathe, Hartman Catharina A., Hoekstra Pieter J., Håberg Asta K., Jönsson Erik G., Kolskår Knut K., Le Hellard StephanieORCID, Lund Martina J., Lundervold Astri J., Lundervold ArvidORCID, Melle Ingrid, Monereo Sánchez Jennifer, Norbom Linn C., Nordvik Jan E.ORCID, Nyberg Lars, Oosterlaan Jaap, Papalino Marco, Papassotiropoulos Andreas, Pergola Giulio, de Quervain Dominique J. F., Richard Geneviève, Sanders Anne-Marthe, Selvaggi Pierluigi, Shumskaya Elena, Steen Vidar M., Tønnesen Siren, Ulrichsen Kristine M., Zwiers Marcel P., Andreassen Ole A.ORCID, Westlye Lars T.ORCID,
Abstract
AbstractThe 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.
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Psychiatry and Mental health,Molecular Biology
Reference75 articles.
1. Burgess N, Maguire EA, O’Keefe J. The human hippocampus and spatial and episodic memory. Neuron. 2002;35:625–41. 2. van Erp TGM, Hibar DP, Rasmussen JM, Glahn DC, Pearlson GD, Andreassen OA et al. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol Psychiatry. 2016; 21: 547–553. 3. Harrison PJ. The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications. Psychopharmacology (Berl). 2004;174:151–62. 4. Leung KK, Barnes J, Ridgway GR, Bartlett JW, Clarkson MJ, Macdonald K. et al. Automated cross-sectional and longitudinal hippocampal volume measurement in mild cognitive impairment and Alzheimer’s disease. Neuroimage. 2010;51:1345–59. 5. Iglesias JE, Augustinack JC, Nguyen K, Player CM, Player A, Wright M et al. A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: application to adaptive segmentation of in vivo MRI. Neuroimage 2015; 115: 117–137.
Cited by
77 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|