Pruning and thresholding approach for methylation risk scores in multi-ancestry populations
Recent efforts have focused on developing methylation risk scores (MRS), a weighted sum of the individual’s DNA methylation (DNAm) values of pre-selected CpG sites. Most of the current MRS approaches that utilize Epigenome-wide association studies (EWAS) summary statistics only include genome-wide s...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2023.2187172 |
| _version_ | 1797678812893282304 |
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| author | Junyu Chen Evan Gatev Todd Everson Karen N. Conneely Nastassja Koen Michael P. Epstein Michael S. Kobor Heather J. Zar Dan J. Stein Anke Hüls |
| author_facet | Junyu Chen Evan Gatev Todd Everson Karen N. Conneely Nastassja Koen Michael P. Epstein Michael S. Kobor Heather J. Zar Dan J. Stein Anke Hüls |
| author_sort | Junyu Chen |
| collection | DOAJ |
| description | Recent efforts have focused on developing methylation risk scores (MRS), a weighted sum of the individual’s DNA methylation (DNAm) values of pre-selected CpG sites. Most of the current MRS approaches that utilize Epigenome-wide association studies (EWAS) summary statistics only include genome-wide significant CpG sites and do not consider co-methylation. New methods that relax the p-value threshold to include more CpG sites and account for the inter-correlation of DNAm might improve the predictive performance of MRS. We paired informed co-methylation pruning with P-value thresholding to generate pruning and thresholding (P+T) MRS and evaluated its performance among multi-ancestry populations. Through simulation studies and real data analyses, we demonstrated that pruning provides an improvement over simple thresholding methods for prediction of phenotypes. We demonstrated that European-derived summary statistics can be used to develop P+T MRS among other populations such as African populations. However, the prediction accuracy of P+T MRS may differ across multi-ancestry population due to environmental/cultural/social differences. |
| first_indexed | 2024-03-11T23:05:22Z |
| format | Article |
| id | doaj.art-4babd77b39d246af9c962658b9fdc9ec |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:22Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-4babd77b39d246af9c962658b9fdc9ec2023-09-21T13:23:13ZengTaylor & Francis GroupEpigenetics1559-22941559-23082023-12-0118110.1080/15592294.2023.21871722187172Pruning and thresholding approach for methylation risk scores in multi-ancestry populationsJunyu Chen0Evan Gatev1Todd Everson2Karen N. Conneely3Nastassja Koen4Michael P. Epstein5Michael S. Kobor6Heather J. Zar7Dan J. Stein8Anke Hüls9Emory UniversityInstitute of Molecular Biology “Acad. Roumen Tsanev”Emory UniversityEmory UniversityUniversity of Cape TownEmory UniversityUniversity of British ColumbiaUniversity of Cape TownUniversity of Cape TownEmory UniversityRecent efforts have focused on developing methylation risk scores (MRS), a weighted sum of the individual’s DNA methylation (DNAm) values of pre-selected CpG sites. Most of the current MRS approaches that utilize Epigenome-wide association studies (EWAS) summary statistics only include genome-wide significant CpG sites and do not consider co-methylation. New methods that relax the p-value threshold to include more CpG sites and account for the inter-correlation of DNAm might improve the predictive performance of MRS. We paired informed co-methylation pruning with P-value thresholding to generate pruning and thresholding (P+T) MRS and evaluated its performance among multi-ancestry populations. Through simulation studies and real data analyses, we demonstrated that pruning provides an improvement over simple thresholding methods for prediction of phenotypes. We demonstrated that European-derived summary statistics can be used to develop P+T MRS among other populations such as African populations. However, the prediction accuracy of P+T MRS may differ across multi-ancestry population due to environmental/cultural/social differences.http://dx.doi.org/10.1080/15592294.2023.2187172epigenetic scorespolygenic dna methylationclumping and thresholdingadmixed population |
| spellingShingle | Junyu Chen Evan Gatev Todd Everson Karen N. Conneely Nastassja Koen Michael P. Epstein Michael S. Kobor Heather J. Zar Dan J. Stein Anke Hüls Pruning and thresholding approach for methylation risk scores in multi-ancestry populations Epigenetics epigenetic scores polygenic dna methylation clumping and thresholding admixed population |
| title | Pruning and thresholding approach for methylation risk scores in multi-ancestry populations |
| title_full | Pruning and thresholding approach for methylation risk scores in multi-ancestry populations |
| title_fullStr | Pruning and thresholding approach for methylation risk scores in multi-ancestry populations |
| title_full_unstemmed | Pruning and thresholding approach for methylation risk scores in multi-ancestry populations |
| title_short | Pruning and thresholding approach for methylation risk scores in multi-ancestry populations |
| title_sort | pruning and thresholding approach for methylation risk scores in multi ancestry populations |
| topic | epigenetic scores polygenic dna methylation clumping and thresholding admixed population |
| url | http://dx.doi.org/10.1080/15592294.2023.2187172 |
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