Prioritization of potential causative genes for schizophrenia in placenta
Abstract Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. W...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38140-1 |
| _version_ | 1797822786088992768 |
|---|---|
| author | Gianluca Ursini Pasquale Di Carlo Sreya Mukherjee Qiang Chen Shizhong Han Jiyoung Kim Maya Deyssenroth Carmen J. Marsit Jia Chen Ke Hao Giovanna Punzi Daniel R. Weinberger |
| author_facet | Gianluca Ursini Pasquale Di Carlo Sreya Mukherjee Qiang Chen Shizhong Han Jiyoung Kim Maya Deyssenroth Carmen J. Marsit Jia Chen Ke Hao Giovanna Punzi Daniel R. Weinberger |
| author_sort | Gianluca Ursini |
| collection | DOAJ |
| description | Abstract Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits. The analyses in the whole sample and stratifying by sex ultimately highlight 139 placenta and schizophrenia-specific risk genes, many being sex-biased; the candidate molecular mechanisms converge on the nutrient-sensing capabilities of placenta and trophoblast invasiveness. These genes also implicate the Coronavirus-pathogenesis pathway and showed increased expression in placentae from a small sample of SARS-CoV-2-positive pregnancies. Investigating placental risk genes for schizophrenia and candidate mechanisms may lead to opportunities for prevention that would not be suggested by study of the brain alone. |
| first_indexed | 2024-03-13T10:13:16Z |
| format | Article |
| id | doaj.art-206d72636ced4f029aed269847f1fd81 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T10:13:16Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-206d72636ced4f029aed269847f1fd812023-05-21T11:20:38ZengNature PortfolioNature Communications2041-17232023-05-0114111710.1038/s41467-023-38140-1Prioritization of potential causative genes for schizophrenia in placentaGianluca Ursini0Pasquale Di Carlo1Sreya Mukherjee2Qiang Chen3Shizhong Han4Jiyoung Kim5Maya Deyssenroth6Carmen J. Marsit7Jia Chen8Ke Hao9Giovanna Punzi10Daniel R. Weinberger11Lieber Institute for Brain Development, Johns Hopkins University Medical CampusLieber Institute for Brain Development, Johns Hopkins University Medical CampusLieber Institute for Brain Development, Johns Hopkins University Medical CampusLieber Institute for Brain Development, Johns Hopkins University Medical CampusLieber Institute for Brain Development, Johns Hopkins University Medical CampusLieber Institute for Brain Development, Johns Hopkins University Medical CampusDepartments of Environmental Medicine and Public Health, Icahn School of Public Health at Mount SinaiDepartments of Environmental Health and Epidemiology, Rollins School of Public Health, Emory UniversityDepartments of Environmental Medicine and Public Health, Icahn School of Public Health at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiLieber Institute for Brain Development, Johns Hopkins University Medical CampusLieber Institute for Brain Development, Johns Hopkins University Medical CampusAbstract Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits. The analyses in the whole sample and stratifying by sex ultimately highlight 139 placenta and schizophrenia-specific risk genes, many being sex-biased; the candidate molecular mechanisms converge on the nutrient-sensing capabilities of placenta and trophoblast invasiveness. These genes also implicate the Coronavirus-pathogenesis pathway and showed increased expression in placentae from a small sample of SARS-CoV-2-positive pregnancies. Investigating placental risk genes for schizophrenia and candidate mechanisms may lead to opportunities for prevention that would not be suggested by study of the brain alone.https://doi.org/10.1038/s41467-023-38140-1 |
| spellingShingle | Gianluca Ursini Pasquale Di Carlo Sreya Mukherjee Qiang Chen Shizhong Han Jiyoung Kim Maya Deyssenroth Carmen J. Marsit Jia Chen Ke Hao Giovanna Punzi Daniel R. Weinberger Prioritization of potential causative genes for schizophrenia in placenta Nature Communications |
| title | Prioritization of potential causative genes for schizophrenia in placenta |
| title_full | Prioritization of potential causative genes for schizophrenia in placenta |
| title_fullStr | Prioritization of potential causative genes for schizophrenia in placenta |
| title_full_unstemmed | Prioritization of potential causative genes for schizophrenia in placenta |
| title_short | Prioritization of potential causative genes for schizophrenia in placenta |
| title_sort | prioritization of potential causative genes for schizophrenia in placenta |
| url | https://doi.org/10.1038/s41467-023-38140-1 |
| work_keys_str_mv | AT gianlucaursini prioritizationofpotentialcausativegenesforschizophreniainplacenta AT pasqualedicarlo prioritizationofpotentialcausativegenesforschizophreniainplacenta AT sreyamukherjee prioritizationofpotentialcausativegenesforschizophreniainplacenta AT qiangchen prioritizationofpotentialcausativegenesforschizophreniainplacenta AT shizhonghan prioritizationofpotentialcausativegenesforschizophreniainplacenta AT jiyoungkim prioritizationofpotentialcausativegenesforschizophreniainplacenta AT mayadeyssenroth prioritizationofpotentialcausativegenesforschizophreniainplacenta AT carmenjmarsit prioritizationofpotentialcausativegenesforschizophreniainplacenta AT jiachen prioritizationofpotentialcausativegenesforschizophreniainplacenta AT kehao prioritizationofpotentialcausativegenesforschizophreniainplacenta AT giovannapunzi prioritizationofpotentialcausativegenesforschizophreniainplacenta AT danielrweinberger prioritizationofpotentialcausativegenesforschizophreniainplacenta |