Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes
van der Meer D, Rokicki J, Kaufmann T, Córdova-Palomera A, Moberget T, Alnæs D, Bettella F, Frei O et al.. Molecular psychiatry, 2018-10-02
Topic: Brain proteins, microglia and lab models
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.
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APA 7th
van der Meer, D., Rokicki, J., Kaufmann, T., Córdova-Palomera, A., Moberget, T., Alnæs, D., et al. (2020). Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes. Molecular psychiatry. https://doi.org/10.1038/s41380-018-0262-7
Vancouver
van der Meer D, Rokicki J, Kaufmann T, Córdova-Palomera A, Moberget T, Alnæs D, et al. Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes. Molecular psychiatry. 2020. doi:10.1038/s41380-018-0262-7. PMID: 30279459.
BibTeX
@article{vandermeer2020-30279459,
author = {van der Meer, D. and Rokicki, J. and Kaufmann, T. and Córdova-Palomera, A. and Moberget, T. and Alnæs, D. and Bettella, F. and Frei, O. and others},
title = {{Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes}},
journal = {Molecular psychiatry},
year = {2020},
doi = {10.1038/s41380-018-0262-7},
pmid = {30279459},
url = {https://doi.org/10.1038/s41380-018-0262-7}
}
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Key findings
- 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.
- We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits.
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Study details
- Participants21,297
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 4 / 4 | 21,297 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30279459) |
| Free to read | 2 / 2 | Free to read |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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