Association and shared biological bases between birth weight and cortical structure
Abstract Associations between birth weight and cortical structural phenotypes have been detected; however, the understanding is incomprehensive, and the potential biological bases are not well defined. Leveraging data from genome-wide association studies, we investigated the associations and the sha...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-03-01
|
| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03294-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850252327991115776 |
|---|---|
| author | Lu Zhang Qiaoyue Ge Zeyuan Sun Rui Zhang Xinxi Li Xiaoli Luo Run Tian Yuheng Cao Chunyan Pu Lin Li Dongsheng Wu Ping Jiang Chuan Yu Chiara Nosarti Chenghan Xiao Zhenmi Liu |
| author_facet | Lu Zhang Qiaoyue Ge Zeyuan Sun Rui Zhang Xinxi Li Xiaoli Luo Run Tian Yuheng Cao Chunyan Pu Lin Li Dongsheng Wu Ping Jiang Chuan Yu Chiara Nosarti Chenghan Xiao Zhenmi Liu |
| author_sort | Lu Zhang |
| collection | DOAJ |
| description | Abstract Associations between birth weight and cortical structural phenotypes have been detected; however, the understanding is incomprehensive, and the potential biological bases are not well defined. Leveraging data from genome-wide association studies, we investigated the associations and the shared transcriptomic, proteomic and cellular bases of birth weight and 13 cortical structural phenotypes. Mendelian randomization analyses were performed to examine associations between birth weight and cortical structure. Downstream transcriptome-wide association study (TWAS), proteome-wide association study (PWAS) and summary-based Mendelian randomization (SMR) analyses were utilized to identify the shared cis-regulated gene expressions and proteins. Finally, cell-type expression-specific integration for complex traits (CELLECT) analyses were conducted to explore the enriched cell types. The Mendelian randomization analyses found positive associations between birth weight and global cortical folding index, intrinsic curvature index, local gyrification index, surface area and volume. Downstream transcriptomic-level TWAS and SMR identified three gene expressions both linked to birth weight and at least one cortical structural phenotype (CNNM2, RABGAP1 and CENPW). Parallel PWAS and SMR analyses at the proteomic level identified four proteins linked to both phenotypes (CNNM2, RAB7L1, RAB5B and PPA2), of which CNNM2 was replicated. CELLECT analyses revealed brain cell types enriched in birth weight, including pericytes, inhibitory GABAergic neurons and cerebrovascular cells. These findings support the importance of early life growth to cortical structure, and suggest underlying transcriptomic, proteomic and cellular bases. These results provide intriguing targets for further research into the mechanisms of cortical development. |
| format | Article |
| id | doaj-art-8fc11d4dfc2c4742bed09c26e4ecb54c |
| institution | OA Journals |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-8fc11d4dfc2c4742bed09c26e4ecb54c2025-08-20T01:57:40ZengNature Publishing GroupTranslational Psychiatry2158-31882025-03-011511910.1038/s41398-025-03294-7Association and shared biological bases between birth weight and cortical structureLu Zhang0Qiaoyue Ge1Zeyuan Sun2Rui Zhang3Xinxi Li4Xiaoli Luo5Run Tian6Yuheng Cao7Chunyan Pu8Lin Li9Dongsheng Wu10Ping Jiang11Chuan Yu12Chiara Nosarti13Chenghan Xiao14Zhenmi Liu15Department of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Radiology, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityAbstract Associations between birth weight and cortical structural phenotypes have been detected; however, the understanding is incomprehensive, and the potential biological bases are not well defined. Leveraging data from genome-wide association studies, we investigated the associations and the shared transcriptomic, proteomic and cellular bases of birth weight and 13 cortical structural phenotypes. Mendelian randomization analyses were performed to examine associations between birth weight and cortical structure. Downstream transcriptome-wide association study (TWAS), proteome-wide association study (PWAS) and summary-based Mendelian randomization (SMR) analyses were utilized to identify the shared cis-regulated gene expressions and proteins. Finally, cell-type expression-specific integration for complex traits (CELLECT) analyses were conducted to explore the enriched cell types. The Mendelian randomization analyses found positive associations between birth weight and global cortical folding index, intrinsic curvature index, local gyrification index, surface area and volume. Downstream transcriptomic-level TWAS and SMR identified three gene expressions both linked to birth weight and at least one cortical structural phenotype (CNNM2, RABGAP1 and CENPW). Parallel PWAS and SMR analyses at the proteomic level identified four proteins linked to both phenotypes (CNNM2, RAB7L1, RAB5B and PPA2), of which CNNM2 was replicated. CELLECT analyses revealed brain cell types enriched in birth weight, including pericytes, inhibitory GABAergic neurons and cerebrovascular cells. These findings support the importance of early life growth to cortical structure, and suggest underlying transcriptomic, proteomic and cellular bases. These results provide intriguing targets for further research into the mechanisms of cortical development.https://doi.org/10.1038/s41398-025-03294-7 |
| spellingShingle | Lu Zhang Qiaoyue Ge Zeyuan Sun Rui Zhang Xinxi Li Xiaoli Luo Run Tian Yuheng Cao Chunyan Pu Lin Li Dongsheng Wu Ping Jiang Chuan Yu Chiara Nosarti Chenghan Xiao Zhenmi Liu Association and shared biological bases between birth weight and cortical structure Translational Psychiatry |
| title | Association and shared biological bases between birth weight and cortical structure |
| title_full | Association and shared biological bases between birth weight and cortical structure |
| title_fullStr | Association and shared biological bases between birth weight and cortical structure |
| title_full_unstemmed | Association and shared biological bases between birth weight and cortical structure |
| title_short | Association and shared biological bases between birth weight and cortical structure |
| title_sort | association and shared biological bases between birth weight and cortical structure |
| url | https://doi.org/10.1038/s41398-025-03294-7 |
| work_keys_str_mv | AT luzhang associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT qiaoyuege associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT zeyuansun associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT ruizhang associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT xinxili associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT xiaoliluo associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT runtian associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT yuhengcao associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT chunyanpu associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT linli associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT dongshengwu associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT pingjiang associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT chuanyu associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT chiaranosarti associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT chenghanxiao associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure AT zhenmiliu associationandsharedbiologicalbasesbetweenbirthweightandcorticalstructure |