Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder
Background Genetic and environmental factors contribute to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). Among genetic risk groups stratified by combinations of Polygenic Risk Score (PRS) deciles for SZ, BD and SZ versus BD, genetic SZ risk groups had high SZ risk and prominent c...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-01-01
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| Series: | BMJ Mental Health |
| Online Access: | https://ebmh.bmj.com/content/27/1/e300936.full |
| _version_ | 1797356810686955520 |
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| author | Toshiki Shioiri Midori Soda Kazutaka Ohi Mihoko Shimada Daisuke Nishizawa Daisuke Fujikane Kentaro Takai Ayumi Kuramitsu Yukimasa Muto Shunsuke Sugiyama Junko Hasegawa Kiyoyuki Kitaichi Kazutaka Ikeda |
| author_facet | Toshiki Shioiri Midori Soda Kazutaka Ohi Mihoko Shimada Daisuke Nishizawa Daisuke Fujikane Kentaro Takai Ayumi Kuramitsu Yukimasa Muto Shunsuke Sugiyama Junko Hasegawa Kiyoyuki Kitaichi Kazutaka Ikeda |
| author_sort | Toshiki Shioiri |
| collection | DOAJ |
| description | Background Genetic and environmental factors contribute to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). Among genetic risk groups stratified by combinations of Polygenic Risk Score (PRS) deciles for SZ, BD and SZ versus BD, genetic SZ risk groups had high SZ risk and prominent cognitive impairments. Furthermore, epigenetic alterations are implicated in these disorders. However, it was unclear whether DNA Methylation Risk Scores (MRSs) for SZ risk derived from blood and brain tissues were associated with SZ risk, particularly the PRS-stratified genetic SZ risk group.Methods Epigenome-wide association studies (EWASs) of SZ risk in whole blood were preliminarily conducted between 66 SZ patients and 30 healthy controls (HCs) and among genetic risk groups (individuals with low genetic risk for SZ and BD in HCs (n=30) and in SZ patients (n=11), genetic BD risk in SZ patients (n=25) and genetic SZ risk in SZ patients (n=30)) stratified by combinations of PRSs for SZ, BD and SZ versus BD. Next, differences in MRSs based on independent EWASs of SZ risk in whole blood, postmortem frontal cortex (FC) and superior temporal gyrus (STG) were investigated among our case‒control and PRS-stratified genetic risk status groups.Results Among case‒control and genetic risk status groups, 33 and 351 genome-wide significant differentially methylated positions (DMPs) associated with SZ were identified, respectively, many of which were hypermethylated. Compared with the low genetic risk in HCs group, the genetic SZ risk in SZ group had 39 genome-wide significant DMPs, while the genetic BD risk in SZ group had only six genome-wide significant DMPs. The MRSs for SZ risk derived from whole blood, FC and STG were higher in our SZ patients than in HCs in whole blood and were particularly higher in the genetic SZ risk in SZ group than in the low genetic risk in HCs and genetic BD risk in SZ groups. Conversely, the MRSs for SZ risk based on our whole-blood EWASs among genetic risk groups were also associated with SZ in the FC and STG. There were no correlations between the MRSs and PRSs.Conclusions These findings suggest that the MRS is a potential genetic marker in understanding SZ, particularly in patients with a genetic SZ risk. |
| first_indexed | 2024-03-08T14:35:14Z |
| format | Article |
| id | doaj.art-6ddb017afb7b4d27a4b1935d9b6f253b |
| institution | Directory Open Access Journal |
| issn | 2755-9734 |
| language | English |
| last_indexed | 2024-03-08T14:35:14Z |
| publishDate | 2024-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Mental Health |
| spelling | doaj.art-6ddb017afb7b4d27a4b1935d9b6f253b2024-01-12T05:05:08ZengBMJ Publishing GroupBMJ Mental Health2755-97342024-01-0127110.1136/bmjment-2023-300936Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorderToshiki Shioiri0Midori Soda1Kazutaka Ohi2Mihoko Shimada3Daisuke Nishizawa4Daisuke Fujikane5Kentaro Takai6Ayumi Kuramitsu7Yukimasa Muto8Shunsuke Sugiyama9Junko Hasegawa10Kiyoyuki Kitaichi11Kazutaka Ikeda121 Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japanassistant department chief1 Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan3 Genome Medical Science Project (Toyama), National Center for Global Health and Medicine (NCGM), Tokyo, Japan5 Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan1 Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan1 Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan1 Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan1 Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan1 Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan5 Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan4 Laboratory of Pharmaceutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan5 Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanBackground Genetic and environmental factors contribute to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). Among genetic risk groups stratified by combinations of Polygenic Risk Score (PRS) deciles for SZ, BD and SZ versus BD, genetic SZ risk groups had high SZ risk and prominent cognitive impairments. Furthermore, epigenetic alterations are implicated in these disorders. However, it was unclear whether DNA Methylation Risk Scores (MRSs) for SZ risk derived from blood and brain tissues were associated with SZ risk, particularly the PRS-stratified genetic SZ risk group.Methods Epigenome-wide association studies (EWASs) of SZ risk in whole blood were preliminarily conducted between 66 SZ patients and 30 healthy controls (HCs) and among genetic risk groups (individuals with low genetic risk for SZ and BD in HCs (n=30) and in SZ patients (n=11), genetic BD risk in SZ patients (n=25) and genetic SZ risk in SZ patients (n=30)) stratified by combinations of PRSs for SZ, BD and SZ versus BD. Next, differences in MRSs based on independent EWASs of SZ risk in whole blood, postmortem frontal cortex (FC) and superior temporal gyrus (STG) were investigated among our case‒control and PRS-stratified genetic risk status groups.Results Among case‒control and genetic risk status groups, 33 and 351 genome-wide significant differentially methylated positions (DMPs) associated with SZ were identified, respectively, many of which were hypermethylated. Compared with the low genetic risk in HCs group, the genetic SZ risk in SZ group had 39 genome-wide significant DMPs, while the genetic BD risk in SZ group had only six genome-wide significant DMPs. The MRSs for SZ risk derived from whole blood, FC and STG were higher in our SZ patients than in HCs in whole blood and were particularly higher in the genetic SZ risk in SZ group than in the low genetic risk in HCs and genetic BD risk in SZ groups. Conversely, the MRSs for SZ risk based on our whole-blood EWASs among genetic risk groups were also associated with SZ in the FC and STG. There were no correlations between the MRSs and PRSs.Conclusions These findings suggest that the MRS is a potential genetic marker in understanding SZ, particularly in patients with a genetic SZ risk.https://ebmh.bmj.com/content/27/1/e300936.full |
| spellingShingle | Toshiki Shioiri Midori Soda Kazutaka Ohi Mihoko Shimada Daisuke Nishizawa Daisuke Fujikane Kentaro Takai Ayumi Kuramitsu Yukimasa Muto Shunsuke Sugiyama Junko Hasegawa Kiyoyuki Kitaichi Kazutaka Ikeda Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder BMJ Mental Health |
| title | Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder |
| title_full | Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder |
| title_fullStr | Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder |
| title_full_unstemmed | Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder |
| title_short | Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder |
| title_sort | genome wide dna methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder |
| url | https://ebmh.bmj.com/content/27/1/e300936.full |
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