Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
Aims Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2020 |
| Country: | España |
| Institution: | INCLIVA |
| Repository: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p15275 |
| Online Access: | https://incliva.portalinvestigacion.com/publicaciones/15275 |
| Access Level: | Open access |
| Keyword: | Environment genetics psychosis schizotypy |
| _version_ | 1878729154803793920 |
|---|---|
| author | Pries, LK |
| author2 | Dal Ferro, GA van Os, J Delespaul, P Kenis, G Lin, BD Luykx, JJ Richards, AL Akdede, B Binbay, T Altinyazar, V Yalincetin, B Gumus-Akay, G Cihan, B Soygur, H Ulas, H Cankurtaran, ES Kaymak, SU Mihaljevic, MM Petrovic, SA Mirjanic, T Bernardo, M Mezquida, G Amoretti, S Bobes, J Saiz, PA Garcia-Portilla, MP Sanjuan, J Aguilar, EJ Santos, JL Jimenez-Lopez, E Arrojo, M Carracedo, A Lopez, G Gonzalez-Penas, J Parellada, M Maric, NP Atbasoglu, C Ucok, A Alptekin, K Saka, MC Arango, C O'Donovan, M Tosato, S Rutten, BPF Guloksuz, S Genetic Risk Outcome Psychosis GRP |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_browse | Aguilar, EJ Akdede, B Alptekin, K Altinyazar, V Amoretti, S Arango, C Arrojo, M Atbasoglu, C Bernardo, M Binbay, T Bobes, J Cankurtaran, ES Carracedo, A Cihan, B Dal Ferro, GA Delespaul, P Garcia-Portilla, MP Genetic Risk Outcome Psychosis GRP Gonzalez-Penas, J Guloksuz, S Gumus-Akay, G Jimenez-Lopez, E Kaymak, SU Kenis, G Lin, BD Lopez, G Luykx, JJ Maric, NP Mezquida, G Mihaljevic, MM Mirjanic, T O'Donovan, M Parellada, M Petrovic, SA Pries, LK Richards, AL Rutten, BPF Saiz, PA Saka, MC Sanjuan, J Santos, JL Soygur, H Tosato, S Ucok, A Ulas, H Yalincetin, B van Os, J |
| author_facet | Pries, LK Dal Ferro, GA van Os, J Delespaul, P Kenis, G Lin, BD Luykx, JJ Richards, AL Akdede, B Binbay, T Altinyazar, V Yalincetin, B Gumus-Akay, G Cihan, B Soygur, H Ulas, H Cankurtaran, ES Kaymak, SU Mihaljevic, MM Petrovic, SA Mirjanic, T Bernardo, M Mezquida, G Amoretti, S Bobes, J Saiz, PA Garcia-Portilla, MP Sanjuan, J Aguilar, EJ Santos, JL Jimenez-Lopez, E Arrojo, M Carracedo, A Lopez, G Gonzalez-Penas, J Parellada, M Maric, NP Atbasoglu, C Ucok, A Alptekin, K Saka, MC Arango, C O'Donovan, M Tosato, S Rutten, BPF Guloksuz, S Genetic Risk Outcome Psychosis GRP |
| author_role | author |
| collection | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| description | Aims Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. Methods The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). Results Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. Conclusions The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_02744d9b9aaf5d94f5f2db5c9409c5d2 |
| institution | INCLIVA |
| instname_str | INCLIVA |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:incliva.fundanetsuite.com:p15275 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | CAMBRIDGE UNIV PRESS |
| publisherStr | CAMBRIDGE UNIV PRESS |
| reponame_str | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| spelling | Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum Pries, LK Dal Ferro, GA van Os, J Delespaul, P Kenis, G Lin, BD Luykx, JJ Richards, AL Akdede, B Binbay, T Altinyazar, V Yalincetin, B Gumus-Akay, G Cihan, B Soygur, H Ulas, H Cankurtaran, ES Kaymak, SU Mihaljevic, MM Petrovic, SA Mirjanic, T Bernardo, M Mezquida, G Amoretti, S Bobes, J Saiz, PA Garcia-Portilla, MP Sanjuan, J Aguilar, EJ Santos, JL Jimenez-Lopez, E Arrojo, M Carracedo, A Lopez, G Gonzalez-Penas, J Parellada, M Maric, NP Atbasoglu, C Ucok, A Alptekin, K Saka, MC Arango, C O'Donovan, M Tosato, S Rutten, BPF Guloksuz, S Genetic Risk Outcome Psychosis GRP Environment genetics psychosis schizotypy Aims Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. Methods The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). Results Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. Conclusions The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype. CAMBRIDGE UNIV PRESS https://incliva.portalinvestigacion.com/publicaciones/15275 |
| spellingShingle | Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum Pries, LK Environment genetics psychosis schizotypy |
| status_str | publishedVersion |
| title | Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum |
| title_full | Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum |
| title_fullStr | Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum |
| title_full_unstemmed | Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum |
| title_short | Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum |
| title_sort | Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum |
| topic | Environment genetics psychosis schizotypy |
| topic_facet | Environment genetics psychosis schizotypy |
| url | https://incliva.portalinvestigacion.com/publicaciones/15275 |