African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer
Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improv...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2020
|
| _version_ | 1826308347745271808 |
|---|---|
| author | Karunamuni, RA Huynh-Le, M-P Fan, CC Thompson, W Eeles, RA Kote-Jarai, Z Muir, K Lophatananon, A Tangen, CM Goodman, PJ Thompson Jr, IM Blot, WJ Zheng, W Kibel, AS Drake, BF Cussenot, O Cancel-Tassin, G Menegaux, F Truong, T Park, JY Lin, H-Y Bensen, JT Fontham, ETH Mohler, JL Taylor, JA Multigner, L Blanchet, P Brureau, L Romana, M Leach, RJ John, EM Fowke, J Bush, WS Aldrich, M Crawford, DC Srivastava, S Cullen, JC Petrovics, G Parent, M-É Hu, JJ Sanderson, M Mills, IG Andreassen, OA Dale, AM Seibert, TM |
| author2 | UKGPCS collaborators |
| author_facet | UKGPCS collaborators Karunamuni, RA Huynh-Le, M-P Fan, CC Thompson, W Eeles, RA Kote-Jarai, Z Muir, K Lophatananon, A Tangen, CM Goodman, PJ Thompson Jr, IM Blot, WJ Zheng, W Kibel, AS Drake, BF Cussenot, O Cancel-Tassin, G Menegaux, F Truong, T Park, JY Lin, H-Y Bensen, JT Fontham, ETH Mohler, JL Taylor, JA Multigner, L Blanchet, P Brureau, L Romana, M Leach, RJ John, EM Fowke, J Bush, WS Aldrich, M Crawford, DC Srivastava, S Cullen, JC Petrovics, G Parent, M-É Hu, JJ Sanderson, M Mills, IG Andreassen, OA Dale, AM Seibert, TM |
| author_sort | Karunamuni, RA |
| collection | OXFORD |
| description | Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans. |
| first_indexed | 2024-03-07T07:18:11Z |
| format | Journal article |
| id | oxford-uuid:484da125-8011-44f4-8865-26627c868f6b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:18:11Z |
| publishDate | 2020 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:484da125-8011-44f4-8865-26627c868f6b2022-09-02T09:18:21ZAfrican-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:484da125-8011-44f4-8865-26627c868f6bEnglishSymplectic ElementsWiley2020Karunamuni, RAHuynh-Le, M-PFan, CCThompson, WEeles, RAKote-Jarai, ZMuir, KLophatananon, ATangen, CMGoodman, PJThompson Jr, IMBlot, WJZheng, WKibel, ASDrake, BFCussenot, OCancel-Tassin, GMenegaux, FTruong, TPark, JYLin, H-YBensen, JTFontham, ETHMohler, JLTaylor, JAMultigner, LBlanchet, PBrureau, LRomana, MLeach, RJJohn, EMFowke, JBush, WSAldrich, MCrawford, DCSrivastava, SCullen, JCPetrovics, GParent, M-ÉHu, JJSanderson, MMills, IGAndreassen, OADale, AMSeibert, TMUKGPCS collaboratorsPRACTICAL ConsortiumPolygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans. |
| spellingShingle | Karunamuni, RA Huynh-Le, M-P Fan, CC Thompson, W Eeles, RA Kote-Jarai, Z Muir, K Lophatananon, A Tangen, CM Goodman, PJ Thompson Jr, IM Blot, WJ Zheng, W Kibel, AS Drake, BF Cussenot, O Cancel-Tassin, G Menegaux, F Truong, T Park, JY Lin, H-Y Bensen, JT Fontham, ETH Mohler, JL Taylor, JA Multigner, L Blanchet, P Brureau, L Romana, M Leach, RJ John, EM Fowke, J Bush, WS Aldrich, M Crawford, DC Srivastava, S Cullen, JC Petrovics, G Parent, M-É Hu, JJ Sanderson, M Mills, IG Andreassen, OA Dale, AM Seibert, TM African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer |
| title | African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer |
| title_full | African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer |
| title_fullStr | African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer |
| title_full_unstemmed | African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer |
| title_short | African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer |
| title_sort | african specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer |
| work_keys_str_mv | AT karunamunira africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT huynhlemp africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT fancc africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT thompsonw africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT eelesra africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT kotejaraiz africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT muirk africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT lophatananona africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT tangencm africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT goodmanpj africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT thompsonjrim africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT blotwj africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT zhengw africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT kibelas africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT drakebf africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT cussenoto africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT canceltassing africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT menegauxf africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT truongt africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT parkjy africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT linhy africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT bensenjt africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT fonthameth africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT mohlerjl africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT taylorja africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT multignerl africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT blanchetp africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT brureaul africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT romanam africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT leachrj africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT johnem africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT fowkej africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT bushws africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT aldrichm africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT crawforddc africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT srivastavas africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT cullenjc africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT petrovicsg africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT parentme africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT hujj africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT sandersonm africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT millsig africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT andreassenoa africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT daleam africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer AT seiberttm africanspecificimprovementofapolygenichazardscoreforageatdiagnosisofprostatecancer |