Assessing thyroid cancer risk using polygenic risk scores
Publisher Copyright: © 2020 National Academy of Sciences. All rights reserved. Genome-wide association studies (GWASs) have identified at least 10 single-nucleotide polymorphisms (SNPs) associated with papillary thyroid cancer (PTC) risk. Most of these SNPs are common variants with small to moderate...
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ftopinvisindi:oai:opinvisindi.is:20.500.11815/3357 2023-11-12T04:19:25+01:00 Assessing thyroid cancer risk using polygenic risk scores Liyanarachchi, Sandya Gudmundsson, Julius Ferkingstad, Egil He, Huiling Jónasson, Jón Gunnlaugur Tragante, Vinicius Asselbergs, Folkert W. Xu, Li Kiemeney, Lambertus A. Netea-Maier, Romana T. Mayordomo, Jose I. Plantinga, Theo S. Hjartarson, Hannes Hrafnkelsson, Jón Sturgis, Erich M. Brock, Pamela Nabhan, Fadi Thorleifsson, Gudmar Ringel, Matthew D. Stefansson, Kari de la Chapelle, Albert Faculty of Medicine Clinical Laboratory Services, Diagnostics and Blood Bank Cancer Center Landspitali - The National University Hospital of Iceland 2020-03-17 6 777719 5997-6002 https://hdl.handle.net/20.500.11815/3357 https://doi.org/10.1073/pnas.1919976117 en eng Proceedings of the National Academy of Sciences of the United States of America; 117(11) http://www.scopus.com/inward/record.url?scp=85081735431&partnerID=8YFLogxK Liyanarachchi , S , Gudmundsson , J , Ferkingstad , E , He , H , Jónasson , J G , Tragante , V , Asselbergs , F W , Xu , L , Kiemeney , L A , Netea-Maier , R T , Mayordomo , J I , Plantinga , T S , Hjartarson , H , Hrafnkelsson , J , Sturgis , E M , Brock , P , Nabhan , F , Thorleifsson , G , Ringel , M D , Stefansson , K & de la Chapelle , A 2020 , ' Assessing thyroid cancer risk using polygenic risk scores ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 117 , no. 11 , pp. 5997-6002 . https://doi.org/10.1073/pnas.1919976117 0027-8424 37679407 06c00575-e07f-489f-9fbc-c93505c1d1df 85081735431 32132206 https://hdl.handle.net/20.500.11815/3357 doi:10.1073/pnas.1919976117 info:eu-repo/semantics/openAccess GWAS Polygenic risk score Risk prediction Thyroid cancer Skjaldkirtill Krabbamein Multidisciplinary /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article 2020 ftopinvisindi https://doi.org/20.500.11815/335710.1073/pnas.1919976117 2023-11-01T23:55:20Z Publisher Copyright: © 2020 National Academy of Sciences. All rights reserved. Genome-wide association studies (GWASs) have identified at least 10 single-nucleotide polymorphisms (SNPs) associated with papillary thyroid cancer (PTC) risk. Most of these SNPs are common variants with small to moderate effect sizes. Here we assessed the combined genetic effects of these variants on PTC risk by using summarized GWAS results to build polygenic risk score (PRS) models in three PTC study groups from Ohio (1,544 patients and 1,593 controls), Iceland (723 patients and 129,556 controls), and the United Kingdom (534 patients and 407,945 controls). A PRS based on the 10 established PTC SNPs showed a stronger predictive power compared with the clinical factors model, with a minimum increase of area under the receiver-operating curve of 5.4 percentage points (P ≤ 1.0 × 10−9). Adding an extended PRS based on 592,475 common variants did not significantly improve the prediction power compared with the 10-SNP model, suggesting that most of the remaining undiscovered genetic risk in thyroid cancer is due to rare, moderate- to high-penetrance variants rather than to common low-penetrance variants. Based on the 10-SNP PRS, individuals in the top decile group of PRSs have a close to sevenfold greater risk (95% CI, 5.4–8.8) compared with the bottom decile group. In conclusion, PRSs based on a small number of common germline variants emphasize the importance of heritable low-penetrance markers in PTC. Peer reviewed Article in Journal/Newspaper Iceland Opin vísindi (Iceland) Proceedings of the National Academy of Sciences 117 11 5997 6002 |
institution |
Open Polar |
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Opin vísindi (Iceland) |
op_collection_id |
ftopinvisindi |
language |
English |
topic |
GWAS Polygenic risk score Risk prediction Thyroid cancer Skjaldkirtill Krabbamein Multidisciplinary |
spellingShingle |
GWAS Polygenic risk score Risk prediction Thyroid cancer Skjaldkirtill Krabbamein Multidisciplinary Liyanarachchi, Sandya Gudmundsson, Julius Ferkingstad, Egil He, Huiling Jónasson, Jón Gunnlaugur Tragante, Vinicius Asselbergs, Folkert W. Xu, Li Kiemeney, Lambertus A. Netea-Maier, Romana T. Mayordomo, Jose I. Plantinga, Theo S. Hjartarson, Hannes Hrafnkelsson, Jón Sturgis, Erich M. Brock, Pamela Nabhan, Fadi Thorleifsson, Gudmar Ringel, Matthew D. Stefansson, Kari de la Chapelle, Albert Assessing thyroid cancer risk using polygenic risk scores |
topic_facet |
GWAS Polygenic risk score Risk prediction Thyroid cancer Skjaldkirtill Krabbamein Multidisciplinary |
description |
Publisher Copyright: © 2020 National Academy of Sciences. All rights reserved. Genome-wide association studies (GWASs) have identified at least 10 single-nucleotide polymorphisms (SNPs) associated with papillary thyroid cancer (PTC) risk. Most of these SNPs are common variants with small to moderate effect sizes. Here we assessed the combined genetic effects of these variants on PTC risk by using summarized GWAS results to build polygenic risk score (PRS) models in three PTC study groups from Ohio (1,544 patients and 1,593 controls), Iceland (723 patients and 129,556 controls), and the United Kingdom (534 patients and 407,945 controls). A PRS based on the 10 established PTC SNPs showed a stronger predictive power compared with the clinical factors model, with a minimum increase of area under the receiver-operating curve of 5.4 percentage points (P ≤ 1.0 × 10−9). Adding an extended PRS based on 592,475 common variants did not significantly improve the prediction power compared with the 10-SNP model, suggesting that most of the remaining undiscovered genetic risk in thyroid cancer is due to rare, moderate- to high-penetrance variants rather than to common low-penetrance variants. Based on the 10-SNP PRS, individuals in the top decile group of PRSs have a close to sevenfold greater risk (95% CI, 5.4–8.8) compared with the bottom decile group. In conclusion, PRSs based on a small number of common germline variants emphasize the importance of heritable low-penetrance markers in PTC. Peer reviewed |
author2 |
Faculty of Medicine Clinical Laboratory Services, Diagnostics and Blood Bank Cancer Center Landspitali - The National University Hospital of Iceland |
format |
Article in Journal/Newspaper |
author |
Liyanarachchi, Sandya Gudmundsson, Julius Ferkingstad, Egil He, Huiling Jónasson, Jón Gunnlaugur Tragante, Vinicius Asselbergs, Folkert W. Xu, Li Kiemeney, Lambertus A. Netea-Maier, Romana T. Mayordomo, Jose I. Plantinga, Theo S. Hjartarson, Hannes Hrafnkelsson, Jón Sturgis, Erich M. Brock, Pamela Nabhan, Fadi Thorleifsson, Gudmar Ringel, Matthew D. Stefansson, Kari de la Chapelle, Albert |
author_facet |
Liyanarachchi, Sandya Gudmundsson, Julius Ferkingstad, Egil He, Huiling Jónasson, Jón Gunnlaugur Tragante, Vinicius Asselbergs, Folkert W. Xu, Li Kiemeney, Lambertus A. Netea-Maier, Romana T. Mayordomo, Jose I. Plantinga, Theo S. Hjartarson, Hannes Hrafnkelsson, Jón Sturgis, Erich M. Brock, Pamela Nabhan, Fadi Thorleifsson, Gudmar Ringel, Matthew D. Stefansson, Kari de la Chapelle, Albert |
author_sort |
Liyanarachchi, Sandya |
title |
Assessing thyroid cancer risk using polygenic risk scores |
title_short |
Assessing thyroid cancer risk using polygenic risk scores |
title_full |
Assessing thyroid cancer risk using polygenic risk scores |
title_fullStr |
Assessing thyroid cancer risk using polygenic risk scores |
title_full_unstemmed |
Assessing thyroid cancer risk using polygenic risk scores |
title_sort |
assessing thyroid cancer risk using polygenic risk scores |
publishDate |
2020 |
url |
https://hdl.handle.net/20.500.11815/3357 https://doi.org/10.1073/pnas.1919976117 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
Proceedings of the National Academy of Sciences of the United States of America; 117(11) http://www.scopus.com/inward/record.url?scp=85081735431&partnerID=8YFLogxK Liyanarachchi , S , Gudmundsson , J , Ferkingstad , E , He , H , Jónasson , J G , Tragante , V , Asselbergs , F W , Xu , L , Kiemeney , L A , Netea-Maier , R T , Mayordomo , J I , Plantinga , T S , Hjartarson , H , Hrafnkelsson , J , Sturgis , E M , Brock , P , Nabhan , F , Thorleifsson , G , Ringel , M D , Stefansson , K & de la Chapelle , A 2020 , ' Assessing thyroid cancer risk using polygenic risk scores ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 117 , no. 11 , pp. 5997-6002 . https://doi.org/10.1073/pnas.1919976117 0027-8424 37679407 06c00575-e07f-489f-9fbc-c93505c1d1df 85081735431 32132206 https://hdl.handle.net/20.500.11815/3357 doi:10.1073/pnas.1919976117 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/20.500.11815/335710.1073/pnas.1919976117 |
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Proceedings of the National Academy of Sciences |
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11 |
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5997 |
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