Genetic Specificity of Hippocampal Subfield Volumes, Relative to Hippocampal Formation, Identified in 2148 Young Adult Twins and Siblings

Hansell, Narelle K., Strike, Lachlan T., van Eijk, Liza, O'Callaghan, Victoria, Martin, Nicholas G., de Zubicaray, Greig I., Thompson, Paul M., Mcmahon, Katie L., and Wright, Margaret J. (2022) Genetic Specificity of Hippocampal Subfield Volumes, Relative to Hippocampal Formation, Identified in 2148 Young Adult Twins and Siblings. Twin Research and Human Genetics, 25 (3). pp. 129-139.

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The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%–72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%–77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%–16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet from a twin study that factors such as home environment may influence hippocampal volumes (albeit, with caveats).

Item ID: 75620
Item Type: Article (Research - C1)
ISSN: 1839-2628
Keywords: Hippocampus, subfields, MRI, twin study, human genetics
Copyright Information: © The Author(s), 2022. Published by Cambridge University Press on behalf of International Society for Twin Studies. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC 486682, NHMRC 1009064
Date Deposited: 03 Aug 2022 08:16
FoR Codes: 52 PSYCHOLOGY > 5203 Clinical and health psychology > 520301 Clinical neuropsychology @ 80%
52 PSYCHOLOGY > 5202 Biological psychology > 520201 Behavioural genetics @ 20%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 50%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280121 Expanding knowledge in psychology @ 50%
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