F50. Genetic Architecture of Hippocampal Subfield Volumes: Shared and Specific Influences

Background The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are known to be differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often found to be impaired in individuals with brain disorders associated with reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given these structural and functional differences, we sought to characterize the subfields’ shared and specific genetic architecture. Methods T1-images (n= 17418, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We calculated the 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. We further ran a genome-wide association analysis on each subfield, correcting for total hippocampal volume. All analyses included age, age2, sex, and intracranial volume as covariates. Results Volumes of all subfields were heritable (h2 ranging from .15 to .29, all p< 2.2 * 10-9) and clustered together (genetic correlations Rg>.41), compared to other brain features. The subiculum and the hippocampal-amygdalar transition area (HATA) showed significant genetic correlation with AD and schizophrenia, respectively. We found 14 independent whole-genome significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were annotated to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. Conclusions Hippocampal subfields have partly distinct genetic determinants, associated with specific biological processes and traits. Taking into account this specificity may aid in furthering our understanding of hippocampal neurobiology and associated disorders.