Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study
Primary open-angle glaucoma (POAG) is a highly heritable disease, with 127 identified risk loci to date. Polygenic risk score (PRS) may provide a clinically useful measure of aggregate genetic burden and improve patient risk stratification. To assess whether a PRS improves prediction of POAG onset i...
Gespeichert in:
| Veröffentlicht in: | Archives of ophthalmology (1960) 2024-04, Vol.142 (4), p.356 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 4 |
| container_start_page | 356 |
| container_title | Archives of ophthalmology (1960) |
| container_volume | 142 |
| creator | Singh, Rishabh K Zhao, Yan Elze, Tobias Fingert, John Gordon, Mae Kass, Michael A Luo, Yuyang Pasquale, Louis R Scheetz, Todd Segrè, Ayellet V Wiggs, Janey L Zebardast, Nazlee |
| description | Primary open-angle glaucoma (POAG) is a highly heritable disease, with 127 identified risk loci to date. Polygenic risk score (PRS) may provide a clinically useful measure of aggregate genetic burden and improve patient risk stratification.
To assess whether a PRS improves prediction of POAG onset in patients with ocular hypertension.
This was a post hoc analysis of the Ocular Hypertension Treatment Study. Data were collected from 22 US sites with a mean (SD) follow-up of 14.0 (6.9) years. A total of 1636 participants were followed up from February 1994 to December 2008; 1077 participants were enrolled in an ancillary genetics study, of which 1009 met criteria for this analysis. PRS was calculated using summary statistics from the largest cross-ancestry POAG meta-analysis, with weights trained using 8 813 496 variants from 449 186 cross-ancestry participants in the UK Biobank. Data were analyzed from July 2022 to December 2023.
From February 1994 to June 2002, participants were randomized to either topical intraocular pressure-lowering medication or close observation. After June 2002, both groups received medication.
Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent areas under the receiver operating characteristic curve were used to compare the predictive performance of multivariable Cox proportional hazards models.
Of 1009 included participants, 562 (55.7%) were female, and the mean (SD) age was 55.9 (9.3) years. The mean (SD) PRS was significantly higher for 350 POAG converters (0.24 [0.95]) compared with 659 nonconverters (-0.12 [1.00]) (P |
| doi_str_mv | 10.1001/jamaophthalmol.2024.0151 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2957167799</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3051071816</sourcerecordid><originalsourceid>FETCH-LOGICAL-c343t-3f1a46694821d57ccce9e5c1e0182b7cbcd0c5001058293ba673b55bd4cb2f013</originalsourceid><addsrcrecordid>eNpdkDtPwzAQgC0Eoqj0LyBLLCwtPjtOnBFV0CIhFdEyW45zoSlJXGxn6L8nFQ8Jbrkbvnt9hFBgM2AMbnemNW6_jVvTtK6ZccaTGQMJJ-SCQ6qmKWTi9LdO5YhMQtixIRRjiZDnZCRUokTC-AVZP7vm8IZdbelLHd7p2jqPgVbO00VjeutaQ1ddwEjrjsYt0pXtG-Pp8rBHH7ELtevoxqOJLXaRrmNfHi7JWWWagJPvPCavD_eb-XL6tFo8zu-eplYkIk5FBSZJ0zxRHEqZWWsxR2kBGSheZLawJbNy-JhJxXNRmDQThZRFmdiCVwzEmNx8zd1799FjiLqtg8WmMR26PmieywzSLMvzAb3-h-5c77vhOi2YBJaBgnSg1BdlvQvBY6X3vm6NP2hg-uhe_3Wvj-710f3QevW9oC9aLH8bf0yLT8pcg2U</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3051071816</pqid></control><display><type>article</type><title>Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study</title><source>MEDLINE</source><source>American Medical Association Journals</source><creator>Singh, Rishabh K ; Zhao, Yan ; Elze, Tobias ; Fingert, John ; Gordon, Mae ; Kass, Michael A ; Luo, Yuyang ; Pasquale, Louis R ; Scheetz, Todd ; Segrè, Ayellet V ; Wiggs, Janey L ; Zebardast, Nazlee</creator><creatorcontrib>Singh, Rishabh K ; Zhao, Yan ; Elze, Tobias ; Fingert, John ; Gordon, Mae ; Kass, Michael A ; Luo, Yuyang ; Pasquale, Louis R ; Scheetz, Todd ; Segrè, Ayellet V ; Wiggs, Janey L ; Zebardast, Nazlee</creatorcontrib><description>Primary open-angle glaucoma (POAG) is a highly heritable disease, with 127 identified risk loci to date. Polygenic risk score (PRS) may provide a clinically useful measure of aggregate genetic burden and improve patient risk stratification.
To assess whether a PRS improves prediction of POAG onset in patients with ocular hypertension.
This was a post hoc analysis of the Ocular Hypertension Treatment Study. Data were collected from 22 US sites with a mean (SD) follow-up of 14.0 (6.9) years. A total of 1636 participants were followed up from February 1994 to December 2008; 1077 participants were enrolled in an ancillary genetics study, of which 1009 met criteria for this analysis. PRS was calculated using summary statistics from the largest cross-ancestry POAG meta-analysis, with weights trained using 8 813 496 variants from 449 186 cross-ancestry participants in the UK Biobank. Data were analyzed from July 2022 to December 2023.
From February 1994 to June 2002, participants were randomized to either topical intraocular pressure-lowering medication or close observation. After June 2002, both groups received medication.
Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent areas under the receiver operating characteristic curve were used to compare the predictive performance of multivariable Cox proportional hazards models.
Of 1009 included participants, 562 (55.7%) were female, and the mean (SD) age was 55.9 (9.3) years. The mean (SD) PRS was significantly higher for 350 POAG converters (0.24 [0.95]) compared with 659 nonconverters (-0.12 [1.00]) (P < .001). POAG risk increased 1.36% (95% CI, 1.08-1.64) with each higher PRS decile, with conversion ranging from 9.52% (95% CI, 7.09-11.95) in the lowest PRS decile to 21.81% (95% CI, 19.37-24.25) in the highest decile. Comparison of low-risk and high-risk PRS tertiles showed a 2.0-fold increase in 20-year POAG risk for participants of European and African ancestries. In the subgroup randomized to delayed treatment, each increase in PRS decile was associated with a 0.52-year (95% CI, 0.01-1.03) decrease in age at diagnosis (P = .047). No significant linear association between PRS and age at POAG diagnosis was present in the early treatment group. Prediction models significantly improved with the addition of PRS as a covariate (C index = 0.77) compared with the Ocular Hypertension Treatment Study baseline model (C index = 0.75) (P < .001). Each 1-SD higher PRS conferred a mean hazard ratio of 1.25 (95% CI, 1.13-1.44) for POAG onset.
Higher PRS was associated with increased risk for POAG in patients with ocular hypertension. The inclusion of a PRS improved the prediction of POAG onset.
ClinicalTrials.gov Identifier: NCT00000125.</description><identifier>ISSN: 2168-6165</identifier><identifier>ISSN: 2168-6173</identifier><identifier>EISSN: 2168-6173</identifier><identifier>DOI: 10.1001/jamaophthalmol.2024.0151</identifier><identifier>PMID: 38483402</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Age ; Diagnosis ; Female ; Genetic Risk Score ; Glaucoma ; Glaucoma, Open-Angle - diagnosis ; Humans ; Hypertension ; Intraocular Pressure ; Male ; Middle Aged ; Ocular Hypertension - diagnosis ; Pharmacists ; Prediction models ; Risk Factors ; Statistical analysis</subject><ispartof>Archives of ophthalmology (1960), 2024-04, Vol.142 (4), p.356</ispartof><rights>Copyright American Medical Association Apr 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c343t-3f1a46694821d57ccce9e5c1e0182b7cbcd0c5001058293ba673b55bd4cb2f013</citedby><cites>FETCH-LOGICAL-c343t-3f1a46694821d57ccce9e5c1e0182b7cbcd0c5001058293ba673b55bd4cb2f013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38483402$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Singh, Rishabh K</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Elze, Tobias</creatorcontrib><creatorcontrib>Fingert, John</creatorcontrib><creatorcontrib>Gordon, Mae</creatorcontrib><creatorcontrib>Kass, Michael A</creatorcontrib><creatorcontrib>Luo, Yuyang</creatorcontrib><creatorcontrib>Pasquale, Louis R</creatorcontrib><creatorcontrib>Scheetz, Todd</creatorcontrib><creatorcontrib>Segrè, Ayellet V</creatorcontrib><creatorcontrib>Wiggs, Janey L</creatorcontrib><creatorcontrib>Zebardast, Nazlee</creatorcontrib><title>Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study</title><title>Archives of ophthalmology (1960)</title><addtitle>JAMA Ophthalmol</addtitle><description>Primary open-angle glaucoma (POAG) is a highly heritable disease, with 127 identified risk loci to date. Polygenic risk score (PRS) may provide a clinically useful measure of aggregate genetic burden and improve patient risk stratification.
To assess whether a PRS improves prediction of POAG onset in patients with ocular hypertension.
This was a post hoc analysis of the Ocular Hypertension Treatment Study. Data were collected from 22 US sites with a mean (SD) follow-up of 14.0 (6.9) years. A total of 1636 participants were followed up from February 1994 to December 2008; 1077 participants were enrolled in an ancillary genetics study, of which 1009 met criteria for this analysis. PRS was calculated using summary statistics from the largest cross-ancestry POAG meta-analysis, with weights trained using 8 813 496 variants from 449 186 cross-ancestry participants in the UK Biobank. Data were analyzed from July 2022 to December 2023.
From February 1994 to June 2002, participants were randomized to either topical intraocular pressure-lowering medication or close observation. After June 2002, both groups received medication.
Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent areas under the receiver operating characteristic curve were used to compare the predictive performance of multivariable Cox proportional hazards models.
Of 1009 included participants, 562 (55.7%) were female, and the mean (SD) age was 55.9 (9.3) years. The mean (SD) PRS was significantly higher for 350 POAG converters (0.24 [0.95]) compared with 659 nonconverters (-0.12 [1.00]) (P < .001). POAG risk increased 1.36% (95% CI, 1.08-1.64) with each higher PRS decile, with conversion ranging from 9.52% (95% CI, 7.09-11.95) in the lowest PRS decile to 21.81% (95% CI, 19.37-24.25) in the highest decile. Comparison of low-risk and high-risk PRS tertiles showed a 2.0-fold increase in 20-year POAG risk for participants of European and African ancestries. In the subgroup randomized to delayed treatment, each increase in PRS decile was associated with a 0.52-year (95% CI, 0.01-1.03) decrease in age at diagnosis (P = .047). No significant linear association between PRS and age at POAG diagnosis was present in the early treatment group. Prediction models significantly improved with the addition of PRS as a covariate (C index = 0.77) compared with the Ocular Hypertension Treatment Study baseline model (C index = 0.75) (P < .001). Each 1-SD higher PRS conferred a mean hazard ratio of 1.25 (95% CI, 1.13-1.44) for POAG onset.
Higher PRS was associated with increased risk for POAG in patients with ocular hypertension. The inclusion of a PRS improved the prediction of POAG onset.
ClinicalTrials.gov Identifier: NCT00000125.</description><subject>Age</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Genetic Risk Score</subject><subject>Glaucoma</subject><subject>Glaucoma, Open-Angle - diagnosis</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Intraocular Pressure</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Ocular Hypertension - diagnosis</subject><subject>Pharmacists</subject><subject>Prediction models</subject><subject>Risk Factors</subject><subject>Statistical analysis</subject><issn>2168-6165</issn><issn>2168-6173</issn><issn>2168-6173</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkDtPwzAQgC0Eoqj0LyBLLCwtPjtOnBFV0CIhFdEyW45zoSlJXGxn6L8nFQ8Jbrkbvnt9hFBgM2AMbnemNW6_jVvTtK6ZccaTGQMJJ-SCQ6qmKWTi9LdO5YhMQtixIRRjiZDnZCRUokTC-AVZP7vm8IZdbelLHd7p2jqPgVbO00VjeutaQ1ddwEjrjsYt0pXtG-Pp8rBHH7ELtevoxqOJLXaRrmNfHi7JWWWagJPvPCavD_eb-XL6tFo8zu-eplYkIk5FBSZJ0zxRHEqZWWsxR2kBGSheZLawJbNy-JhJxXNRmDQThZRFmdiCVwzEmNx8zd1799FjiLqtg8WmMR26PmieywzSLMvzAb3-h-5c77vhOi2YBJaBgnSg1BdlvQvBY6X3vm6NP2hg-uhe_3Wvj-710f3QevW9oC9aLH8bf0yLT8pcg2U</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Singh, Rishabh K</creator><creator>Zhao, Yan</creator><creator>Elze, Tobias</creator><creator>Fingert, John</creator><creator>Gordon, Mae</creator><creator>Kass, Michael A</creator><creator>Luo, Yuyang</creator><creator>Pasquale, Louis R</creator><creator>Scheetz, Todd</creator><creator>Segrè, Ayellet V</creator><creator>Wiggs, Janey L</creator><creator>Zebardast, Nazlee</creator><general>American Medical Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20240401</creationdate><title>Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study</title><author>Singh, Rishabh K ; Zhao, Yan ; Elze, Tobias ; Fingert, John ; Gordon, Mae ; Kass, Michael A ; Luo, Yuyang ; Pasquale, Louis R ; Scheetz, Todd ; Segrè, Ayellet V ; Wiggs, Janey L ; Zebardast, Nazlee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c343t-3f1a46694821d57ccce9e5c1e0182b7cbcd0c5001058293ba673b55bd4cb2f013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Age</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Genetic Risk Score</topic><topic>Glaucoma</topic><topic>Glaucoma, Open-Angle - diagnosis</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Intraocular Pressure</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Ocular Hypertension - diagnosis</topic><topic>Pharmacists</topic><topic>Prediction models</topic><topic>Risk Factors</topic><topic>Statistical analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Singh, Rishabh K</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Elze, Tobias</creatorcontrib><creatorcontrib>Fingert, John</creatorcontrib><creatorcontrib>Gordon, Mae</creatorcontrib><creatorcontrib>Kass, Michael A</creatorcontrib><creatorcontrib>Luo, Yuyang</creatorcontrib><creatorcontrib>Pasquale, Louis R</creatorcontrib><creatorcontrib>Scheetz, Todd</creatorcontrib><creatorcontrib>Segrè, Ayellet V</creatorcontrib><creatorcontrib>Wiggs, Janey L</creatorcontrib><creatorcontrib>Zebardast, Nazlee</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Archives of ophthalmology (1960)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Singh, Rishabh K</au><au>Zhao, Yan</au><au>Elze, Tobias</au><au>Fingert, John</au><au>Gordon, Mae</au><au>Kass, Michael A</au><au>Luo, Yuyang</au><au>Pasquale, Louis R</au><au>Scheetz, Todd</au><au>Segrè, Ayellet V</au><au>Wiggs, Janey L</au><au>Zebardast, Nazlee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study</atitle><jtitle>Archives of ophthalmology (1960)</jtitle><addtitle>JAMA Ophthalmol</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>142</volume><issue>4</issue><spage>356</spage><pages>356-</pages><issn>2168-6165</issn><issn>2168-6173</issn><eissn>2168-6173</eissn><abstract>Primary open-angle glaucoma (POAG) is a highly heritable disease, with 127 identified risk loci to date. Polygenic risk score (PRS) may provide a clinically useful measure of aggregate genetic burden and improve patient risk stratification.
To assess whether a PRS improves prediction of POAG onset in patients with ocular hypertension.
This was a post hoc analysis of the Ocular Hypertension Treatment Study. Data were collected from 22 US sites with a mean (SD) follow-up of 14.0 (6.9) years. A total of 1636 participants were followed up from February 1994 to December 2008; 1077 participants were enrolled in an ancillary genetics study, of which 1009 met criteria for this analysis. PRS was calculated using summary statistics from the largest cross-ancestry POAG meta-analysis, with weights trained using 8 813 496 variants from 449 186 cross-ancestry participants in the UK Biobank. Data were analyzed from July 2022 to December 2023.
From February 1994 to June 2002, participants were randomized to either topical intraocular pressure-lowering medication or close observation. After June 2002, both groups received medication.
Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent areas under the receiver operating characteristic curve were used to compare the predictive performance of multivariable Cox proportional hazards models.
Of 1009 included participants, 562 (55.7%) were female, and the mean (SD) age was 55.9 (9.3) years. The mean (SD) PRS was significantly higher for 350 POAG converters (0.24 [0.95]) compared with 659 nonconverters (-0.12 [1.00]) (P < .001). POAG risk increased 1.36% (95% CI, 1.08-1.64) with each higher PRS decile, with conversion ranging from 9.52% (95% CI, 7.09-11.95) in the lowest PRS decile to 21.81% (95% CI, 19.37-24.25) in the highest decile. Comparison of low-risk and high-risk PRS tertiles showed a 2.0-fold increase in 20-year POAG risk for participants of European and African ancestries. In the subgroup randomized to delayed treatment, each increase in PRS decile was associated with a 0.52-year (95% CI, 0.01-1.03) decrease in age at diagnosis (P = .047). No significant linear association between PRS and age at POAG diagnosis was present in the early treatment group. Prediction models significantly improved with the addition of PRS as a covariate (C index = 0.77) compared with the Ocular Hypertension Treatment Study baseline model (C index = 0.75) (P < .001). Each 1-SD higher PRS conferred a mean hazard ratio of 1.25 (95% CI, 1.13-1.44) for POAG onset.
Higher PRS was associated with increased risk for POAG in patients with ocular hypertension. The inclusion of a PRS improved the prediction of POAG onset.
ClinicalTrials.gov Identifier: NCT00000125.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>38483402</pmid><doi>10.1001/jamaophthalmol.2024.0151</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2168-6165 |
| ispartof | Archives of ophthalmology (1960), 2024-04, Vol.142 (4), p.356 |
| issn | 2168-6165 2168-6173 2168-6173 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2957167799 |
| source | MEDLINE; American Medical Association Journals |
| subjects | Age Diagnosis Female Genetic Risk Score Glaucoma Glaucoma, Open-Angle - diagnosis Humans Hypertension Intraocular Pressure Male Middle Aged Ocular Hypertension - diagnosis Pharmacists Prediction models Risk Factors Statistical analysis |
| title | Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T12%3A42%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Polygenic%20Risk%20Scores%20for%20Glaucoma%20Onset%20in%20the%20Ocular%20Hypertension%20Treatment%20Study&rft.jtitle=Archives%20of%20ophthalmology%20(1960)&rft.au=Singh,%20Rishabh%20K&rft.date=2024-04-01&rft.volume=142&rft.issue=4&rft.spage=356&rft.pages=356-&rft.issn=2168-6165&rft.eissn=2168-6173&rft_id=info:doi/10.1001/jamaophthalmol.2024.0151&rft_dat=%3Cproquest_cross%3E3051071816%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3051071816&rft_id=info:pmid/38483402&rfr_iscdi=true |