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

• Published in: Nature genetics Vol. 55; no. 7; pp. 1126 - 1137
• Main Authors: Liu, Nana, Zhang, Longjiang, Tian, Tian, Cheng, Jingliang, Zhang, Bing, Qiu, Shijun, Geng, Zuojun, Cui, Guangbin, Zhang, Quan, Liao, Weihua, Yu, Yongqiang, Zhang, Hui, Gao, Bo, Xu, Xiaojun, Han, Tong, Yao, Zhenwei, Qin, Wen, Liu, Feng, Liang, Meng, Xu, Qiang, Fu, Jilian, Xu, Jiayuan, Zhu, Wenzhen, Zhang, Peng, Li, Wei, Shi, Dapeng, Wang, Caihong, Lui, Su, Yan, Zhihan, Chen, Feng, Li, Jiance, Zhang, Jing, Wang, Dawei, Shen, Wen, Miao, Yanwei, Xian, Junfang, Gao, Jia-Hong, Zhang, Xiaochu, Li, Mulin Jun, Xu, Kai, Zuo, Xi-Nian, Wang, Meiyun, Ye, Zhaoxiang, Yu, Chunshui
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2023; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 631/378/368; Agriculture; Alzheimer's disease; Animal Genetics and Genomics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cognition; Disorders; Gene Function; Gene mapping; Genetic diversity; Genetic variance; Genetics; Genome-wide association studies; Genomes; Hippocampus; Human Genetics; Kinases; Medical imaging; Mental disorders; Meta-analysis; Neuroimaging; Polygenic inheritance; Population genetics; Populations; Proteins; Wnt protein; X chromosomes
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/s41588-023-01425-8

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 cross-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 new associations. Common genetic variants have similar effects on hippocampal traits across ancestries, although ancestry-specific associations exist. Cross-ancestry analysis improves the fine-mapping precision and the prediction performance of polygenic scores in under-represented populations. These genetic variants are enriched for Wnt signaling and neuron differentiation and affect cognition, emotion and neuropsychiatric disorders. These findings may provide insight into the genetic architectures of hippocampal and subfield volumes. Genome-wide association meta-analyses in populations of East Asian and European ancestries identify variant–trait associations for 44 hippocampal traits and provide insight into the genetic architectures of hippocampal and subfield volumes.