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Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample
A recent publication reported an exciting polygenic effect of schizophrenia (SCZ) risk variants, identified by a large genome-wide association study (GWAS), on total brain and white matter volumes in schizophrenic patients and, even more prominently, in healthy subjects. The aim of the present work...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944630/ https://www.ncbi.nlm.nih.gov/pubmed/24548877 http://dx.doi.org/10.1038/tp.2013.126 |
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author | Papiol, S Mitjans, M Assogna, F Piras, F Hammer, C Caltagirone, C Arias, B Ehrenreich, H Spalletta, G |
author_facet | Papiol, S Mitjans, M Assogna, F Piras, F Hammer, C Caltagirone, C Arias, B Ehrenreich, H Spalletta, G |
author_sort | Papiol, S |
collection | PubMed |
description | A recent publication reported an exciting polygenic effect of schizophrenia (SCZ) risk variants, identified by a large genome-wide association study (GWAS), on total brain and white matter volumes in schizophrenic patients and, even more prominently, in healthy subjects. The aim of the present work was to replicate and then potentially extend these findings. According to the original publication, polygenic risk scores—using single nucleotide polymorphism (SNP) information of SCZ GWAS—(polygenic SCZ risk scores; PSS) were calculated in 122 healthy subjects, enrolled in a structural magnetic resonance imaging (MRI) study. These scores were computed based on P-values and odds ratios available through the Psychiatric GWAS Consortium. In addition, polygenic white matter scores (PWM) were calculated, using the respective SNP subset in the original publication. None of the polygenic scores, either PSS or PWM, were found to be associated with total brain, white matter or gray matter volume in our replicate sample. Minor differences between the original and the present study that might have contributed to lack of reproducibility (but unlikely explain it fully), are number of subjects, ethnicity, age distribution, array technology, SNP imputation quality and MRI scanner type. In contrast to the original publication, our results do not reveal the slightest signal of association of the described sets of GWAS-identified SCZ risk variants with brain volumes in adults. Caution is indicated in interpreting studies building on polygenic risk scores without replication sample. |
format | Online Article Text |
id | pubmed-3944630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39446302014-03-06 Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample Papiol, S Mitjans, M Assogna, F Piras, F Hammer, C Caltagirone, C Arias, B Ehrenreich, H Spalletta, G Transl Psychiatry Original Article A recent publication reported an exciting polygenic effect of schizophrenia (SCZ) risk variants, identified by a large genome-wide association study (GWAS), on total brain and white matter volumes in schizophrenic patients and, even more prominently, in healthy subjects. The aim of the present work was to replicate and then potentially extend these findings. According to the original publication, polygenic risk scores—using single nucleotide polymorphism (SNP) information of SCZ GWAS—(polygenic SCZ risk scores; PSS) were calculated in 122 healthy subjects, enrolled in a structural magnetic resonance imaging (MRI) study. These scores were computed based on P-values and odds ratios available through the Psychiatric GWAS Consortium. In addition, polygenic white matter scores (PWM) were calculated, using the respective SNP subset in the original publication. None of the polygenic scores, either PSS or PWM, were found to be associated with total brain, white matter or gray matter volume in our replicate sample. Minor differences between the original and the present study that might have contributed to lack of reproducibility (but unlikely explain it fully), are number of subjects, ethnicity, age distribution, array technology, SNP imputation quality and MRI scanner type. In contrast to the original publication, our results do not reveal the slightest signal of association of the described sets of GWAS-identified SCZ risk variants with brain volumes in adults. Caution is indicated in interpreting studies building on polygenic risk scores without replication sample. Nature Publishing Group 2014-02 2014-02-18 /pmc/articles/PMC3944630/ /pubmed/24548877 http://dx.doi.org/10.1038/tp.2013.126 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Papiol, S Mitjans, M Assogna, F Piras, F Hammer, C Caltagirone, C Arias, B Ehrenreich, H Spalletta, G Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample |
title | Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample |
title_full | Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample |
title_fullStr | Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample |
title_full_unstemmed | Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample |
title_short | Polygenic determinants of white matter volume derived from GWAS lack reproducibility in a replicate sample |
title_sort | polygenic determinants of white matter volume derived from gwas lack reproducibility in a replicate sample |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944630/ https://www.ncbi.nlm.nih.gov/pubmed/24548877 http://dx.doi.org/10.1038/tp.2013.126 |
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