The genetic architecture of brainstem structures

Abstract

The brainstem houses numerous nuclei and tracts that serve vital functions. Genome-wide associations with brainstem substructure volumes have been explored in European individuals, yet other ancestries remain under-represented. Here, we conduct cross-ancestry genome-wide association meta-analyses in 103,098 individuals for brainstem and 78,062 individuals for eight substructure volumes, including 7094 Chinese Han individuals. We identify 713 locus-trait associations with brainstem and substructure volumes at P < 5.56 ×10^-9, comprising 569 new associations. Two associations show different effect sizes, while 496 associations have similar effect sizes between ancestries. We prioritize 186 genes associated with brainstem volumetric traits. We find both shared and distinct genetic loci, genes, and pathways for midbrain, pons, and medulla volumes, along with the shared genetic architectures related to disease phenotypes and physiological functions. The results provide new insights into the genetic architectures of brainstem and substructure volumes and their genetic associations with brainstem physiologies and pathologies.

Affiliated Institutions

• Fudan University CN
• Affiliated Hospital of Guizhou Medical University CN
• First Affiliated Hospital of Anhui Medical University CN
• Tianjin Medical University CN
• First Affiliated Hospital of Guangzhou University of Chinese Medicine CN
• Xiangya Hospital Central South University CN
• Lanzhou University Second Hospital CN
• First Affiliated Hospital of Wenzhou Medical University CN
• Beijing Normal University CN
• Nanjing Drum Tower Hospital CN
• West China Hospital of Sichuan University CN
• Hainan General Hospital CN
• Shanxi Medical University CN
• Chinese Institute for Brain Research CN
• First Affiliated Hospital of Dalian Medical University CN
• Tongji Hospital CN
• Huashan Hospital CN
• Second Affiliated Hospital of Zhejiang University CN
• Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University CN
• Hainan Medical University CN
• Capital Medical University CN
• Dalian Medical University CN
• Zhengzhou University CN
• First Hospital of Shanxi Medical University CN
• Peking University CN
• Henan Provincial People's Hospital CN
• Lanzhou University CN
• Yuhuangding Hospital CN
• Tianjin First Center Hospital CN
• University of Science and Technology of China CN
• Second Hospital of Hebei Medical University CN
• Nanjing General Hospital of Nanjing Military Command CN
• Nanjing University CN
• Guiyang Medical University CN
• Central South University CN
• Qilu Hospital of Shandong University CN
• Hebei Medical University CN
• Tianjin Huanhu Hospital CN
• Air Force Medical University CN
• Tianjin Medical University Cancer Institute and Hospital CN
• Institute of Psychology, Chinese Academy of Sciences CN
• Tianjin Medical University General Hospital CN
• Anhui Medical University CN
• Huazhong University of Science and Technology CN
• First Affiliated Hospital of Zhengzhou University CN
• Wenzhou Medical University CN
• Beijing Tongren Hospital CN

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