Brain scans from 21297 individuals reveal the genetic architecture of hippocampal subfield volumes
Dennis van der Meer,
Nhat Trung Doan,
Christine L. Brandt,
Jan K Buitelaar,
Marjolein van Donkelaar,
Erlend S. Dørum,
Stephen V. Faraone,
Simon E. Fisher D.Phil.,
Catharina A. Hartman,
Pieter J Hoekstra,
Asta K. Håberg,
Erik G. Jönsson,
Knut K. Kolskår,
Stephanie Le Hellard,
Martina J. Lund,
Astri J. Lundervold,
Jennifer Monereo Sánchez,
Linn C. Norbom,
Jan E. Nordvik,
Dominique J.F. de Quervain,
Vidar M. Steen,
Kristine M. Ulrichsen Cand.Psychol.,
Marcel P. Zwiers,
Ole A. Andreassen Lars,
Lars T. Westlye
Posted 11 Apr 2018
bioRxiv DOI: 10.1101/299578 (published DOI: 10.1038/s41380-018-0262-7)
Posted 11 Apr 2018
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=21297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, covarying for total hippocampal volume. We further calculated the single nucleotide polymorphism (SNP)-based heritability of twelve 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 .14 to .27, all p< 1x10-16) and clustered together based on their genetic correlations compared to 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.
- Downloaded 679 times
- Download rankings, all-time:
- Site-wide: 24,330 out of 100,904
- In genetics: 1,478 out of 5,022
- Year to date:
- Site-wide: 78,554 out of 100,904
- Since beginning of last month:
- Site-wide: 78,995 out of 100,904
Downloads over time
Distribution of downloads per paper, site-wide
- 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!