The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes
Abstract Brain anatomy plays a key role in complex behaviors and mental disorders that are sexually divergent. While our understanding of the sex differences in the brain anatomy remains relatively limited, particularly of the underlying genetic and molecular mechanisms that contribute to these diff...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-01-01
|
| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03223-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585343568707584 |
|---|---|
| author | Yuanyuan Gui Geyu Zhou Shuya Cui Hongyu Li Hui Lu Hongyu Zhao |
| author_facet | Yuanyuan Gui Geyu Zhou Shuya Cui Hongyu Li Hui Lu Hongyu Zhao |
| author_sort | Yuanyuan Gui |
| collection | DOAJ |
| description | Abstract Brain anatomy plays a key role in complex behaviors and mental disorders that are sexually divergent. While our understanding of the sex differences in the brain anatomy remains relatively limited, particularly of the underlying genetic and molecular mechanisms that contribute to these differences. We performed the largest study of sex differences in brain volumes (N = 33,208) by examining sex differences both in the raw brain volumes and after controlling the whole brain volumes. Genetic correlation analysis revealed sex differences only in the left amygdala. We compared transcriptome differences between males and females using data from GTEx and characterized cell-type compositions using GTEx bulk amygdala RNA-seq data and LIBD amygdala single-cell reference profiles. We also constructed polygenic risk scores (PRS) to investigate sex-specific genetic correlations between left amygdala volume and mental disorders (N = 25,576~105,318) of Psychiatric Genomics Consortium and other traits of UKB (N = 347,996). Although there were pronounced sex differences in brain volumes, there was no difference in the heritability between sexes. There was a significant sex-specific genetic correlation between male and female left amygdala. We identified sex-differentiated genetic effects of PRSs for schizophrenia on left amygdala volume, as well as significant sex-differentiated genetic correlations between PRSs of left amygdala and six traits in UKB. We also found several sex-differentially expressed genes in the amygdala. These findings not only advanced the current knowledge of genetic basis of sex differences in brain anatomy, but also presented an important clue for future research on the mechanism of sex differences in mental disorders and targeted treatments. |
| format | Article |
| id | doaj-art-2fd5ad2882e44a599ff331beaa85344c |
| institution | Kabale University |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-2fd5ad2882e44a599ff331beaa85344c2025-01-26T12:53:34ZengNature Publishing GroupTranslational Psychiatry2158-31882025-01-011511710.1038/s41398-025-03223-8The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumesYuanyuan Gui0Geyu Zhou1Shuya Cui2Hongyu Li3Hui Lu4Hongyu Zhao5Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityProgram in Computational Biology and Bioinformatics, Yale UniversitySJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityDepartment of Biostatistics, Yale School of Public Health, Yale UniversitySJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityProgram in Computational Biology and Bioinformatics, Yale UniversityAbstract Brain anatomy plays a key role in complex behaviors and mental disorders that are sexually divergent. While our understanding of the sex differences in the brain anatomy remains relatively limited, particularly of the underlying genetic and molecular mechanisms that contribute to these differences. We performed the largest study of sex differences in brain volumes (N = 33,208) by examining sex differences both in the raw brain volumes and after controlling the whole brain volumes. Genetic correlation analysis revealed sex differences only in the left amygdala. We compared transcriptome differences between males and females using data from GTEx and characterized cell-type compositions using GTEx bulk amygdala RNA-seq data and LIBD amygdala single-cell reference profiles. We also constructed polygenic risk scores (PRS) to investigate sex-specific genetic correlations between left amygdala volume and mental disorders (N = 25,576~105,318) of Psychiatric Genomics Consortium and other traits of UKB (N = 347,996). Although there were pronounced sex differences in brain volumes, there was no difference in the heritability between sexes. There was a significant sex-specific genetic correlation between male and female left amygdala. We identified sex-differentiated genetic effects of PRSs for schizophrenia on left amygdala volume, as well as significant sex-differentiated genetic correlations between PRSs of left amygdala and six traits in UKB. We also found several sex-differentially expressed genes in the amygdala. These findings not only advanced the current knowledge of genetic basis of sex differences in brain anatomy, but also presented an important clue for future research on the mechanism of sex differences in mental disorders and targeted treatments.https://doi.org/10.1038/s41398-025-03223-8 |
| spellingShingle | Yuanyuan Gui Geyu Zhou Shuya Cui Hongyu Li Hui Lu Hongyu Zhao The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes Translational Psychiatry |
| title | The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes |
| title_full | The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes |
| title_fullStr | The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes |
| title_full_unstemmed | The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes |
| title_short | The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes |
| title_sort | left amygdala is genetically sexually dimorphic multi omics analysis of structural mri volumes |
| url | https://doi.org/10.1038/s41398-025-03223-8 |
| work_keys_str_mv | AT yuanyuangui theleftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT geyuzhou theleftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT shuyacui theleftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT hongyuli theleftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT huilu theleftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT hongyuzhao theleftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT yuanyuangui leftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT geyuzhou leftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT shuyacui leftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT hongyuli leftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT huilu leftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes AT hongyuzhao leftamygdalaisgeneticallysexuallydimorphicmultiomicsanalysisofstructuralmrivolumes |