Association analysis between polygenic risk scores and traits: practical guidelines and tutorial with an illustrative data set of schizophrenia
Most methodological Polygenic Risk Score (PRS)-related papers explain the laborious process of computing the PRS in great depth. Afterwards, as a last step, it is generally described that to test a possible association between a PRS and a trait of interest, an analysis through regression models (lin...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
|
| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1621972/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849231573688254464 |
|---|---|
| author | Itziar Irigoien Patricia Mas-Bermejo Patricia Mas-Bermejo Sergi Papiol Sergi Papiol Sergi Papiol Neus Barrantes-Vidal Neus Barrantes-Vidal Neus Barrantes-Vidal Araceli Rosa Araceli Rosa Araceli Rosa Concepción Arenas |
| author_facet | Itziar Irigoien Patricia Mas-Bermejo Patricia Mas-Bermejo Sergi Papiol Sergi Papiol Sergi Papiol Neus Barrantes-Vidal Neus Barrantes-Vidal Neus Barrantes-Vidal Araceli Rosa Araceli Rosa Araceli Rosa Concepción Arenas |
| author_sort | Itziar Irigoien |
| collection | DOAJ |
| description | Most methodological Polygenic Risk Score (PRS)-related papers explain the laborious process of computing the PRS in great depth. Afterwards, as a last step, it is generally described that to test a possible association between a PRS and a trait of interest, an analysis through regression models (linear or logistic, depending on data type) should be carried out adjusting for covariates (e.g., sex, age, clinical information, or genetic ancestry-based Principal Components). When covariates are included, measurements such as the increment on the variance explained by the addition of the PRS to the model or the significance of the PRS term are usually reported. However, the association study between PRSs and a trait is a complex concern that requires proper modeling and analysis, since interactions and validation conditions represent crucial aspects. Even though excellent papers explain how to use and interpret the results obtained with such regression models, sometimes important information from the previously calculated PRS may be lost, partly due to the automation of analyses. With this guide, we intend to fill a gap in association studies between PRSs and a trait and to facilitate the analysis, obtaining statistically correct results. It contains a motivating real data case analyzed exhaustively to illustrate how to face a real analysis. Besides, it is accompanied by four examples, called Working Examples, which present different situations the researcher may encounter along with the R code for analyzing all these data sets and the corresponding application of the steps in this guide. |
| format | Article |
| id | doaj-art-7d0f14a513fe4f0b8bf196a530932a1a |
| institution | Kabale University |
| issn | 1664-0640 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj-art-7d0f14a513fe4f0b8bf196a530932a1a2025-08-21T05:27:23ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-08-011610.3389/fpsyt.2025.16219721621972Association analysis between polygenic risk scores and traits: practical guidelines and tutorial with an illustrative data set of schizophreniaItziar Irigoien0Patricia Mas-Bermejo1Patricia Mas-Bermejo2Sergi Papiol3Sergi Papiol4Sergi Papiol5Neus Barrantes-Vidal6Neus Barrantes-Vidal7Neus Barrantes-Vidal8Araceli Rosa9Araceli Rosa10Araceli Rosa11Concepción Arenas12Department of Computation and Artificial Intelligence, Euskal Herriko Unibertsitatea (UPV/EHU), Donostia, SpainZoology and Biological Anthropology Section of the Evolutionary Biology, Ecology and Environmental Sciences Department, Universitat de Barcelona (UB), Barcelona, SpainInstitut de Biomedicina de la UB (IBUB), Barcelona, SpainCentre for Biomedical Network on Mental Health (CIBERSAM), Instituto Salud Carlos III, Barcelona, SpainInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyMax Planck Institute of Psychiatry, Munich, GermanyInstitut de Biomedicina de la UB (IBUB), Barcelona, SpainDepartment of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Barcelona, SpainSant Pere Claver- Fundació Sanitària, Barcelona, SpainZoology and Biological Anthropology Section of the Evolutionary Biology, Ecology and Environmental Sciences Department, Universitat de Barcelona (UB), Barcelona, SpainInstitut de Biomedicina de la UB (IBUB), Barcelona, SpainCentre for Biomedical Network on Mental Health (CIBERSAM), Instituto Salud Carlos III, Barcelona, SpainStatistics Section of the Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB), Barcelona, SpainMost methodological Polygenic Risk Score (PRS)-related papers explain the laborious process of computing the PRS in great depth. Afterwards, as a last step, it is generally described that to test a possible association between a PRS and a trait of interest, an analysis through regression models (linear or logistic, depending on data type) should be carried out adjusting for covariates (e.g., sex, age, clinical information, or genetic ancestry-based Principal Components). When covariates are included, measurements such as the increment on the variance explained by the addition of the PRS to the model or the significance of the PRS term are usually reported. However, the association study between PRSs and a trait is a complex concern that requires proper modeling and analysis, since interactions and validation conditions represent crucial aspects. Even though excellent papers explain how to use and interpret the results obtained with such regression models, sometimes important information from the previously calculated PRS may be lost, partly due to the automation of analyses. With this guide, we intend to fill a gap in association studies between PRSs and a trait and to facilitate the analysis, obtaining statistically correct results. It contains a motivating real data case analyzed exhaustively to illustrate how to face a real analysis. Besides, it is accompanied by four examples, called Working Examples, which present different situations the researcher may encounter along with the R code for analyzing all these data sets and the corresponding application of the steps in this guide.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1621972/fullpolygenic risk scorestatistical analysiscovariatesschizophreniapsychotic-like experiences |
| spellingShingle | Itziar Irigoien Patricia Mas-Bermejo Patricia Mas-Bermejo Sergi Papiol Sergi Papiol Sergi Papiol Neus Barrantes-Vidal Neus Barrantes-Vidal Neus Barrantes-Vidal Araceli Rosa Araceli Rosa Araceli Rosa Concepción Arenas Association analysis between polygenic risk scores and traits: practical guidelines and tutorial with an illustrative data set of schizophrenia Frontiers in Psychiatry polygenic risk score statistical analysis covariates schizophrenia psychotic-like experiences |
| title | Association analysis between polygenic risk scores and traits: practical guidelines and tutorial with an illustrative data set of schizophrenia |
| title_full | Association analysis between polygenic risk scores and traits: practical guidelines and tutorial with an illustrative data set of schizophrenia |
| title_fullStr | Association analysis between polygenic risk scores and traits: practical guidelines and tutorial with an illustrative data set of schizophrenia |
| title_full_unstemmed | Association analysis between polygenic risk scores and traits: practical guidelines and tutorial with an illustrative data set of schizophrenia |
| title_short | Association analysis between polygenic risk scores and traits: practical guidelines and tutorial with an illustrative data set of schizophrenia |
| title_sort | association analysis between polygenic risk scores and traits practical guidelines and tutorial with an illustrative data set of schizophrenia |
| topic | polygenic risk score statistical analysis covariates schizophrenia psychotic-like experiences |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1621972/full |
| work_keys_str_mv | AT itziaririgoien associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT patriciamasbermejo associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT patriciamasbermejo associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT sergipapiol associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT sergipapiol associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT sergipapiol associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT neusbarrantesvidal associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT neusbarrantesvidal associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT neusbarrantesvidal associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT aracelirosa associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT aracelirosa associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT aracelirosa associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia AT concepcionarenas associationanalysisbetweenpolygenicriskscoresandtraitspracticalguidelinesandtutorialwithanillustrativedatasetofschizophrenia |