Common genetic variants contribute to heritability of age at onset of schizophrenia
Abstract Schizophrenia (SCZ) is a complex disorder that typically arises in late adolescence or early adulthood. Age at onset (AAO) of SCZ is associated with long-term outcomes of the disease. We explored the genetic architecture of AAO with a genome-wide association study (GWAS), heritability, poly...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-06-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02508-0 |
| _version_ | 1827602775762010112 |
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| author | Ester Sada-Fuente Selena Aranda Sergi Papiol Urs Heilbronner María Dolores Moltó Eduardo J. Aguilar Javier González-Peñas Álvaro Andreu-Bernabeu Celso Arango Benedicto Crespo-Facorro Ana González-Pinto Lourdes Fañanás Barbara Arias Julio Bobes Javier Costas Lourdes Martorell Thomas G. Schulze Janos L. Kalman Elisabet Vilella Gerard Muntané |
| author_facet | Ester Sada-Fuente Selena Aranda Sergi Papiol Urs Heilbronner María Dolores Moltó Eduardo J. Aguilar Javier González-Peñas Álvaro Andreu-Bernabeu Celso Arango Benedicto Crespo-Facorro Ana González-Pinto Lourdes Fañanás Barbara Arias Julio Bobes Javier Costas Lourdes Martorell Thomas G. Schulze Janos L. Kalman Elisabet Vilella Gerard Muntané |
| author_sort | Ester Sada-Fuente |
| collection | DOAJ |
| description | Abstract Schizophrenia (SCZ) is a complex disorder that typically arises in late adolescence or early adulthood. Age at onset (AAO) of SCZ is associated with long-term outcomes of the disease. We explored the genetic architecture of AAO with a genome-wide association study (GWAS), heritability, polygenic risk score (PRS), and copy number variant (CNV) analyses in 4 740 subjects of European ancestry. Although no genome-wide significant locus was identified, SNP-based heritability of AAO was estimated to be between 17 and 21%, indicating a moderate contribution of common variants. We also performed cross-trait PRS analyses with a set of mental disorders and identified a negative association between AAO and common variants for SCZ, childhood maltreatment and attention-deficit/hyperactivity disorder. We also investigated the role of copy number variants (CNVs) in AAO and found an association with the length and number of deletions (P-value = 0.03), whereas the presence of CNVs previously reported in SCZ was not associated with earlier onset. To our knowledge, this is the largest GWAS of AAO of SCZ to date in individuals from European ancestry, and the first study to determine the involvement of common variants in the heritability of AAO. Finally, we evidenced the role played by higher SCZ load in determining AAO but discarded the role of pathogenic CNVs. Altogether, these results shed light on the genetic architecture of AAO, which needs to be confirmed with larger studies. |
| first_indexed | 2024-03-09T05:25:21Z |
| format | Article |
| id | doaj.art-79165bf273b64d24b7788777a2d08f5e |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-09T05:25:21Z |
| publishDate | 2023-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-79165bf273b64d24b7788777a2d08f5e2023-12-03T12:37:10ZengNature Publishing GroupTranslational Psychiatry2158-31882023-06-011311910.1038/s41398-023-02508-0Common genetic variants contribute to heritability of age at onset of schizophreniaEster Sada-Fuente0Selena Aranda1Sergi Papiol2Urs Heilbronner3María Dolores Moltó4Eduardo J. Aguilar5Javier González-Peñas6Álvaro Andreu-Bernabeu7Celso Arango8Benedicto Crespo-Facorro9Ana González-Pinto10Lourdes Fañanás11Barbara Arias12Julio Bobes13Javier Costas14Lourdes Martorell15Thomas G. Schulze16Janos L. Kalman17Elisabet Vilella18Gerard Muntané19Hospital Universitari Institut Pere Mata, Institut d’Investigació Sanitària Pere Virgili (IISPV), Department of Psychiatry, Universitat Rovira i Virgili (URV)Hospital Universitari Institut Pere Mata, Institut d’Investigació Sanitària Pere Virgili (IISPV), Department of Psychiatry, Universitat Rovira i Virgili (URV)Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, Ludwig Maximilian University of MunichInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, Ludwig Maximilian University of MunichCentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Psychiatric Genetics Group, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Servizo Galego de Saúde (SERGAS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS)Hospital Universitari Institut Pere Mata, Institut d’Investigació Sanitària Pere Virgili (IISPV), Department of Psychiatry, Universitat Rovira i Virgili (URV)Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, Ludwig Maximilian University of MunichInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, Ludwig Maximilian University of MunichHospital Universitari Institut Pere Mata, Institut d’Investigació Sanitària Pere Virgili (IISPV), Department of Psychiatry, Universitat Rovira i Virgili (URV)Hospital Universitari Institut Pere Mata, Institut d’Investigació Sanitària Pere Virgili (IISPV), Department of Psychiatry, Universitat Rovira i Virgili (URV)Abstract Schizophrenia (SCZ) is a complex disorder that typically arises in late adolescence or early adulthood. Age at onset (AAO) of SCZ is associated with long-term outcomes of the disease. We explored the genetic architecture of AAO with a genome-wide association study (GWAS), heritability, polygenic risk score (PRS), and copy number variant (CNV) analyses in 4 740 subjects of European ancestry. Although no genome-wide significant locus was identified, SNP-based heritability of AAO was estimated to be between 17 and 21%, indicating a moderate contribution of common variants. We also performed cross-trait PRS analyses with a set of mental disorders and identified a negative association between AAO and common variants for SCZ, childhood maltreatment and attention-deficit/hyperactivity disorder. We also investigated the role of copy number variants (CNVs) in AAO and found an association with the length and number of deletions (P-value = 0.03), whereas the presence of CNVs previously reported in SCZ was not associated with earlier onset. To our knowledge, this is the largest GWAS of AAO of SCZ to date in individuals from European ancestry, and the first study to determine the involvement of common variants in the heritability of AAO. Finally, we evidenced the role played by higher SCZ load in determining AAO but discarded the role of pathogenic CNVs. Altogether, these results shed light on the genetic architecture of AAO, which needs to be confirmed with larger studies.https://doi.org/10.1038/s41398-023-02508-0 |
| spellingShingle | Ester Sada-Fuente Selena Aranda Sergi Papiol Urs Heilbronner María Dolores Moltó Eduardo J. Aguilar Javier González-Peñas Álvaro Andreu-Bernabeu Celso Arango Benedicto Crespo-Facorro Ana González-Pinto Lourdes Fañanás Barbara Arias Julio Bobes Javier Costas Lourdes Martorell Thomas G. Schulze Janos L. Kalman Elisabet Vilella Gerard Muntané Common genetic variants contribute to heritability of age at onset of schizophrenia Translational Psychiatry |
| title | Common genetic variants contribute to heritability of age at onset of schizophrenia |
| title_full | Common genetic variants contribute to heritability of age at onset of schizophrenia |
| title_fullStr | Common genetic variants contribute to heritability of age at onset of schizophrenia |
| title_full_unstemmed | Common genetic variants contribute to heritability of age at onset of schizophrenia |
| title_short | Common genetic variants contribute to heritability of age at onset of schizophrenia |
| title_sort | common genetic variants contribute to heritability of age at onset of schizophrenia |
| url | https://doi.org/10.1038/s41398-023-02508-0 |
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