Trans-ancestry genome-wide association meta-analyses of hippocampal and subfield volumes

Abstract The hippocampus is critical for memory and cognition and neuropsychiatric disorders, and its subfields differ in cytoarchitecture, function and disease vulnerability. The genetic architectures of hippocampal and subfield volumes have been studied in individuals of European ancestry; however, the results cannot explain for inter-ancestry differences in their associations with cognitive abilities and brain disorders. Here, we conduct trans-ancestry genome-wide association meta-analyses in 65,821 individuals for hippocampal volume and 39,007 for subfield volumes, including 7,039 individuals of East Asian ancestry. We identify 539 locus-trait associations at P < 5×10− 8 for 44 hippocampal volumetric traits, including 161 novel associations and 41 novel loci. Trans-ancestry analysis improves the precision of fine-mapping mainly caused by the inter-ancestry difference in linkage disequilibrium and can enhance the prediction performance of polygenic scores in under-represented population by including hundreds of individuals from this population. Genetic variants associated with hippocampal and subfield volumes are enriched for neurogenesis and Wnt signaling and also affect cognition, emotion and neuropsychiatric disorders, such as Alzheimer's disease, schizophrenia, and depression. Our results highlight the value of trans-ancestry analysis in the investigation of genetic architectures of human traits.