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 architecture and function. Genome-wide association studies on hippocampal and subfield volumes are mainly conducted in European populations; however other ancestral populations are under-represented. Here, we conduct trans-ancestry genome-wide association meta-analyses in 65,791 individuals for hippocampal volume and 38,977 for subfield volumes, including 7,009 individuals of East Asian ancestry. We identify 339 variant-trait associations at P < 1.13 × 10⁻⁹ for 44 hippocampal traits, including 23 novel associations. Common genetic variants have similar effects on hippocampal traits across ancestries, though ancestry-specific associations exist. Trans-ancestry analysis improves the fine mapping precision and the prediction performance of polygenic score in under-represented population. These genetic variants are enriched for Wnt signaling and neuron differentiation and affect cognition, emotion, and neuropsychiatric disorders. Our results highlight the value of trans-ancestry analysis in the investigation of genetic architectures of human traits.