{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:26:09Z","timestamp":1792808769587,"version":"4.5.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"11","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA16058"],"award-info":[{"award-number":["P30CA16058"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P01CA124570"],"award-info":[{"award-number":["P01CA124570"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,3,17]]},"abstract":"<jats:p>\n                    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 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2264 1.0 \u00d7 10\n                    <jats:sup>\u22129<\/jats:sup>\n                    ). 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\u20138.8) 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1919976117","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T20:19:42Z","timestamp":1583353182000},"page":"5997-6002","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":60,"title":["Assessing thyroid cancer risk using polygenic risk scores"],"prefix":"10.1073","volume":"117","author":[{"given":"Sandya","family":"Liyanarachchi","sequence":"first","affiliation":[{"name":"Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"},{"name":"Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Gudmundsson","sequence":"additional","affiliation":[{"name":"Department of Population Genomics, deCODE genetics\/Amgen Inc., 101 Reykjavik, Iceland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egil","family":"Ferkingstad","sequence":"additional","affiliation":[{"name":"Department of Population Genomics, deCODE genetics\/Amgen Inc., 101 Reykjavik, Iceland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"He","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"},{"name":"Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon G.","family":"Jonasson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Landspitali-University Hospital, 101 Reykjavik, Iceland;"},{"name":"Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland;"},{"name":"Department of Epidemiology, The Icelandic Cancer Registry, 105 Reykjavik, Iceland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius","family":"Tragante","sequence":"additional","affiliation":[{"name":"Department of Population Genomics, deCODE genetics\/Amgen Inc., 101 Reykjavik, Iceland;"},{"name":"Department of Cardiology, Heart and Lung Division, University Medical Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert W.","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart and Lung Division, University Medical Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands;"},{"name":"Durrer Center for Cardiovascular Research, Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands;"},{"name":"Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, WC1E 6BT London, United Kingdom;"},{"name":"Farr Institute of Health Informatics Research, University College London, NW1 2DA London, United Kingdom;"},{"name":"Institute of Health Informatics, University College London, NW1 2DA London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;"},{"name":"Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambertus A.","family":"Kiemeney","sequence":"additional","affiliation":[{"name":"Radboud Institute for Health Sciences, Radboud University Medical Centre, 6500HB Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana T.","family":"Netea-Maier","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Radboud Institute for Health Sciences, Radboud University Medical Centre, 6500HB Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose I.","family":"Mayordomo","sequence":"additional","affiliation":[{"name":"UCHealth Diane O\u2019Connor Thompson Breast Center, University of Colorado Hospital, Aurora, CO 80045;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo S.","family":"Plantinga","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500HB Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Hjartarson","sequence":"additional","affiliation":[{"name":"Head&amp;Neck Surgery Department, Landspitali-University Hospital, 101 Reykjavik, Iceland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Hrafnkelsson","sequence":"additional","affiliation":[{"name":"Department of Oncology, Landspitali-University Hospital, 101 Reykjavik, Iceland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich M.","family":"Sturgis","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;"},{"name":"Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Brock","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Nabhan","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudmar","family":"Thorleifsson","sequence":"additional","affiliation":[{"name":"Department of Population Genomics, deCODE genetics\/Amgen Inc., 101 Reykjavik, Iceland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Ringel","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Stefansson","sequence":"additional","affiliation":[{"name":"Department of Population Genomics, deCODE genetics\/Amgen Inc., 101 Reykjavik, Iceland;"},{"name":"Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9345-9248","authenticated-orcid":false,"given":"Albert","family":"de la Chapelle","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"},{"name":"Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,3,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/S0140-6736(13)60109-9","article-title":"Progress in molecular-based management of differentiated thyroid cancer","volume":"381","author":"Xing M.","year":"2013","unstructured":"M. Xing, B. R. Haugen, M. Schlumberger, Progress in molecular-based management of differentiated thyroid cancer. Lancet 381, 1058\u20131069 (2013).","journal-title":"Lancet"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: Towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","author":"Stenson P. D.","year":"2017","unstructured":"P. D. Stenson ., The Human Gene Mutation Database: Towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum. Genet. 136, 665\u2013677 (2017).","journal-title":"Hum. Genet."},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fmolb.2018.00076","article-title":"Molecular diagnostics in clinical oncology","volume":"5","author":"Sokolenko A. P.","year":"2018","unstructured":"A. P. Sokolenko, E. N. Imyanitov, Molecular diagnostics in clinical oncology. Front. Mol. Biosci. 5, 76 (2018).","journal-title":"Front. Mol. Biosci."},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1089\/thy.2013.0102","article-title":"Cumulative risk impact of five genetic variants associated with papillary thyroid carcinoma","volume":"23","author":"Liyanarachchi S.","year":"2013","unstructured":"S. Liyanarachchi ., Cumulative risk impact of five genetic variants associated with papillary thyroid carcinoma. Thyroid 23, 1532\u20131540 (2013).","journal-title":"Thyroid"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1002\/pros.23037","article-title":"Prediction of individual genetic risk to prostate cancer using a polygenic score","volume":"75","author":"Szulkin R.","year":"2015","unstructured":"R. Szulkin .; Australian Prostate Cancer BioResource; Practical Consortium, Prediction of individual genetic risk to prostate cancer using a polygenic score. Prostate 75, 1467\u20131474 (2015).","journal-title":"Prostate"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1001\/jamaoncol.2016.1025","article-title":"Breast cancer risk from modifiable and nonmodifiable risk factors among white women in the United States","volume":"2","author":"Maas P.","year":"2016","unstructured":"P. Maas ., Breast cancer risk from modifiable and nonmodifiable risk factors among white women in the United States. JAMA Oncol. 2, 1295\u20131302 (2016).","journal-title":"JAMA Oncol."},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.ajhg.2018.04.001","article-title":"Association of polygenic risk scores for multiple cancers in a phenome-wide study: Results from the Michigan Genomics Initiative","volume":"102","author":"Fritsche L. G.","year":"2018","unstructured":"L. G. Fritsche ., Association of polygenic risk scores for multiple cancers in a phenome-wide study: Results from the Michigan Genomics Initiative. Am. J. Hum. Genet. 102, 1048\u20131061 (2018).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ajhg.2018.11.002","article-title":"ABCTB Investigators; kConFab\/AOCS Investigators; NBCS Collaborators, Polygenic risk scores for prediction of breast cancer and breast cancer subtypes","volume":"104","author":"Mavaddat N.","year":"2019","unstructured":"N. Mavaddat .; ABCTB Investigators; kConFab\/AOCS Investigators; NBCS Collaborators, Polygenic risk scores for prediction of breast cancer and breast cancer subtypes. Am. J. Hum. Genet. 104, 21\u201334 (2019).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1093\/jnci\/86.21.1600","article-title":"Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands","volume":"86","author":"Goldgar D. E.","year":"1994","unstructured":"D. E. Goldgar, D. F. Easton, L. A. Cannon-Albright, M. H. Skolnick, Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J. Natl. Cancer Inst. 86, 1600\u20131608 (1994).","journal-title":"J. Natl. Cancer Inst."},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/1097-0215(200102)9999:9999<::AID-IJC1147>3.0.CO;2-C","article-title":"Modification of cancer risks in offspring by sibling and parental cancers from 2,112,616 nuclear families","volume":"92","author":"Dong C.","year":"2001","unstructured":"C. Dong, K. Hemminki, Modification of cancer risks in offspring by sibling and parental cancers from 2,112,616 nuclear families. Int. J. Cancer 92, 144\u2013150 (2001).","journal-title":"Int. J. Cancer"},{"key":"e_1_3_4_11_2","first-page":"733","article-title":"The genetic epidemiology of cancer: Interpreting family and twin studies and their implications for molecular genetic approaches","volume":"10","author":"Risch N.","year":"2001","unstructured":"N. Risch, The genetic epidemiology of cancer: Interpreting family and twin studies and their implications for molecular genetic approaches. Cancer Epidemiol. Biomarkers Prev. 10, 733\u2013741 (2001).","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/ng.339","article-title":"Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations","volume":"41","author":"Gudmundsson J.","year":"2009","unstructured":"J. Gudmundsson ., Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat. Genet. 41, 460\u2013464 (2009).","journal-title":"Nat. Genet."},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/ng.1046","article-title":"Discovery of common variants associated with low TSH levels and thyroid cancer risk","volume":"44","author":"Gudmundsson J.","year":"2012","unstructured":"J. Gudmundsson ., Discovery of common variants associated with low TSH levels and thyroid cancer risk. Nat. Genet. 44, 319\u2013322 (2012).","journal-title":"Nat. Genet."},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"E1674","DOI":"10.1210\/jc.2013-1941","article-title":"Genome-wide association study on differentiated thyroid cancer","volume":"98","author":"K\u00f6hler A.","year":"2013","unstructured":"A. K\u00f6hler ., Genome-wide association study on differentiated thyroid cancer. J. Clin. Endocrinol. Metab. 98, E1674\u2013E1681 (2013).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"15966","DOI":"10.1038\/ncomms15966","article-title":"Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer","volume":"8","author":"Son H.-Y.","year":"2017","unstructured":"H.-Y. Son ., Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer. Nat. Commun. 8, 15966 (2017).","journal-title":"Nat. Commun."},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"14517","DOI":"10.1038\/ncomms14517","article-title":"A genome-wide association study yields five novel thyroid cancer risk loci","volume":"8","author":"Gudmundsson J.","year":"2017","unstructured":"J. Gudmundsson ., A genome-wide association study yields five novel thyroid cancer risk loci. Nat. Commun. 8, 14517 (2017).","journal-title":"Nat. Commun."},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"E2084","DOI":"10.1210\/jc.2014-1734","article-title":"Novel genome-wide association study-based candidate loci for differentiated thyroid cancer risk","volume":"99","author":"Figlioli G.","year":"2014","unstructured":"G. Figlioli ., Novel genome-wide association study-based candidate loci for differentiated thyroid cancer risk. J. Clin. Endocrinol. Metab. 99, E2084\u2013E2092 (2014).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1158\/1055-9965.EPI-15-0652","article-title":"A comprehensive meta-analysis of case-control association studies to evaluate polymorphisms associated with the risk of differentiated thyroid carcinoma","volume":"25","author":"Figlioli G.","year":"2016","unstructured":"G. Figlioli ., A comprehensive meta-analysis of case-control association studies to evaluate polymorphisms associated with the risk of differentiated thyroid carcinoma. Cancer Epidemiol. Biomarkers Prev. 25, 700\u2013713 (2016).","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1002\/ijc.29557","article-title":"Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations","volume":"137","author":"Mancikova V.","year":"2015","unstructured":"V. Mancikova ., Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations. Int. J. Cancer 137, 1870\u20131878 (2015).","journal-title":"Int. J. Cancer"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"8922","DOI":"10.1038\/srep08922","article-title":"Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk","volume":"5","author":"Figlioli G.","year":"2015","unstructured":"G. Figlioli ., Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk. Sci. Rep. 5, 8922 (2015).","journal-title":"Sci. Rep."},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"4384","DOI":"10.1210\/jc.2017-02439","article-title":"Genome-wide association study reveals distinct genetic susceptibility of thyroid nodules from thyroid cancer","volume":"103","author":"Hwangbo Y.","year":"2018","unstructured":"Y. Hwangbo ., Genome-wide association study reveals distinct genetic susceptibility of thyroid nodules from thyroid cancer. J. Clin. Endocrinol. Metab. 103, 4384\u20134394 (2018).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","unstructured":"C. Bycroft . Genome-wide genetic data on \u223c500 000 UK Biobank participants. bioRxiv:10.1101\/166298 (20 July 2017).","DOI":"10.1101\/166298"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft C.","year":"2018","unstructured":"C. Bycroft ., The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203\u2013209 (2018).","journal-title":"Nature"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.ajhg.2015.09.001","article-title":"Modeling linkage disequilibrium increases accuracy of polygenic risk scores","volume":"97","author":"Vilhj\u00e1lmsson B. J.","year":"2015","unstructured":"B. J. Vilhj\u00e1lmsson .; Schizophrenia Working Group of the Psychiatric Genomics Consortium, Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study, Modeling linkage disequilibrium increases accuracy of polygenic risk scores. Am. J. Hum. Genet. 97, 576\u2013592 (2015).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"7213","DOI":"10.1038\/ncomms8213","article-title":"Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma","volume":"6","author":"Swaminathan B.","year":"2015","unstructured":"B. Swaminathan ., Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma. Nat. Commun. 6, 7213 (2015).","journal-title":"Nat. Commun."},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/ng.2609","article-title":"Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis","volume":"45","author":"Fingerlin T. E.","year":"2013","unstructured":"T. E. Fingerlin ., Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat. Genet. 45, 613\u2013620 (2013).","journal-title":"Nat. Genet."},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ajhg.2018.11.008","article-title":"Leveraging polygenic functional enrichment to improve GWAS power","volume":"104","author":"Kichaev G.","year":"2019","unstructured":"G. Kichaev ., Leveraging polygenic functional enrichment to improve GWAS power. Am. J. Hum. Genet. 104, 65\u201375 (2019).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/ng.3892","article-title":"Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes","volume":"49","author":"McKay J. D.","year":"2017","unstructured":"J. D. McKay .; SpiroMeta Consortium, Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes. Nat. Genet. 49, 1126\u20131132 (2017).","journal-title":"Nat. Genet."},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/ng.3826","article-title":"Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer","volume":"49","author":"Phelan C. M.","year":"2017","unstructured":"C. M. Phelan .; AOCS study group; EMBRACE Study; GEMO Study Collaborators; HEBON Study; KConFab Investigators; OPAL study group, Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat. Genet. 49, 680\u2013691 (2017).","journal-title":"Nat. Genet."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature24284","article-title":"Association analysis identifies 65 new breast cancer risk loci","volume":"551","author":"Michailidou K.","year":"2017","unstructured":"K. Michailidou .; NBCS Collaborators; ABCTB Investigators; ConFab\/AOCS Investigators, Association analysis identifies 65 new breast cancer risk loci. Nature 551, 92\u201394 (2017).","journal-title":"Nature"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1073\/pnas.1119675109","article-title":"The mystery of missing heritability: Genetic interactions create phantom heritability","volume":"109","author":"Zuk O.","year":"2012","unstructured":"O. Zuk, E. Hechter, S. R. Sunyaev, E. S. Lander, The mystery of missing heritability: Genetic interactions create phantom heritability. Proc. Natl. Acad. Sci. U.S.A. 109, 1193\u20131198 (2012).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"e1008222","DOI":"10.1371\/journal.pgen.1008222","article-title":"Solving the missing heritability problem","volume":"15","author":"Young A. I.","year":"2019","unstructured":"A. I. Young, Solving the missing heritability problem. PLoS Genet. 15, e1008222 (2019).","journal-title":"PLoS Genet."},{"key":"e_1_3_4_33_2","unstructured":"P. Wainschtein . Recovery of trait heritability from whole genome sequence data. bioRxiv:10.1101\/588020 (25 March 2019)."},{"key":"e_1_3_4_34_2","first-page":"2157","article-title":"Genetic heterogeneity in familial nonmedullary thyroid carcinoma: Exclusion of linkage to RET, MNG1, and TCO in 56 families","volume":"84","author":"Lesueur F.","year":"1999","unstructured":"F. Lesueur .; NMTC Consortium, Genetic heterogeneity in familial nonmedullary thyroid carcinoma: Exclusion of linkage to RET, MNG1, and TCO in 56 families. J. Clin. Endocrinol. Metab. 84, 2157\u20132162 (1999).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"E973","DOI":"10.1210\/jc.2012-3823","article-title":"SRGAP1 is a candidate gene for papillary thyroid carcinoma susceptibility","volume":"98","author":"He H.","year":"2013","unstructured":"H. He ., SRGAP1 is a candidate gene for papillary thyroid carcinoma susceptibility. J. Clin. Endocrinol. Metab. 98, E973\u2013E980 (2013).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"e61920","DOI":"10.1371\/journal.pone.0061920","article-title":"Ultra-rare mutation in long-range enhancer predisposes to thyroid carcinoma with high penetrance","volume":"8","author":"He H.","year":"2013","unstructured":"H. He ., Ultra-rare mutation in long-range enhancer predisposes to thyroid carcinoma with high penetrance. PLoS One 8, e61920 (2013).","journal-title":"PLoS One"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"10566","DOI":"10.1038\/srep10566","article-title":"A germline mutation in SRRM2, a splicing factor gene, is implicated in papillary thyroid carcinoma predisposition","volume":"5","author":"Tomsic J.","year":"2015","unstructured":"J. Tomsic ., A germline mutation in SRRM2, a splicing factor gene, is implicated in papillary thyroid carcinoma predisposition. Sci. Rep. 5, 10566 (2015).","journal-title":"Sci. Rep."},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1089\/thy.2018.0736","article-title":"Identification of rare variants predisposing to thyroid cancer","volume":"29","author":"Wang Y.","year":"2019","unstructured":"Y. Wang ., Identification of rare variants predisposing to thyroid cancer. Thyroid 29, 946\u2013955 (2019).","journal-title":"Thyroid"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.1260825","article-title":"Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions","volume":"347","author":"Tomasetti C.","year":"2015","unstructured":"C. Tomasetti, B. Vogelstein, Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347, 78\u201381 (2015).","journal-title":"Science"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1126\/science.aaf9011","article-title":"Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention","volume":"355","author":"Tomasetti C.","year":"2017","unstructured":"C. Tomasetti, L. Li, B. Vogelstein, Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science 355, 1330\u20131334 (2017).","journal-title":"Science"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"djv036","DOI":"10.1093\/jnci\/djv036","article-title":"Prediction of breast cancer risk based on profiling with common genetic variants","volume":"107","author":"Mavaddat N.","year":"2015","unstructured":"N. Mavaddat ., Prediction of breast cancer risk based on profiling with common genetic variants. J. Natl. Cancer Inst. 107, djv036 (2015).","journal-title":"J. Natl. Cancer Inst."},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/gim.2016.101","article-title":"Modeling the prevention of colorectal cancer from the combined impact of host and behavioral risk factors","volume":"19","author":"Frampton M.","year":"2017","unstructured":"M. Frampton, R. S. Houlston, Modeling the prevention of colorectal cancer from the combined impact of host and behavioral risk factors. Genet. Med. 19, 314\u2013321 (2017).","journal-title":"Genet. Med."},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1093\/annonc\/mdw003","article-title":"Personalized testing based on polygenic risk score is promising for more efficient population-based screening programs for common oncological diseases","volume":"27","author":"Radice P.","year":"2016","unstructured":"P. Radice, P. D. P. Pharoah, P. Peterlongo, Personalized testing based on polygenic risk score is promising for more efficient population-based screening programs for common oncological diseases. Ann. Oncol. 27, 369\u2013370 (2016).","journal-title":"Ann. Oncol."},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1136\/jmedgenet-2018-105313","article-title":"Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study","volume":"55","author":"Yang X.","year":"2018","unstructured":"X. Yang ., Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study. J. Med. Genet. 55, 546\u2013554 (2018).","journal-title":"J. Med. Genet."},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"979","DOI":"10.4158\/EP171805.RA","article-title":"Role of molecular markers in thyroid nodule management: Then and now","volume":"23","author":"Nikiforov Y. E.","year":"2017","unstructured":"Y. E. Nikiforov, Role of molecular markers in thyroid nodule management: Then and now. Endocr. Pract. 23, 979\u2013988 (2017).","journal-title":"Endocr. Pract."},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1002\/cncr.31245","article-title":"Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules","volume":"124","author":"Nikiforova M. N.","year":"2018","unstructured":"M. N. Nikiforova ., Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer 124, 1682\u20131690 (2018).","journal-title":"Cancer"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1089\/thy.2018.0733","article-title":"Afirma gene sequencing classifier compared with gene expression classifier in indeterminate thyroid nodules","volume":"29","author":"Endo M.","year":"2019","unstructured":"M. Endo ., Afirma gene sequencing classifier compared with gene expression classifier in indeterminate thyroid nodules. Thyroid 29, 1115\u20131124 (2019).","journal-title":"Thyroid"},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S2213-2600(15)00283-0","article-title":"Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): A genetic association study in UK Biobank","volume":"3","author":"Wain L. V.","year":"2015","unstructured":"L. V. Wain .; UK Brain Expression Consortium (UKBEC); OxGSK Consortium, Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): A genetic association study in UK Biobank. Lancet Respir. Med. 3, 769\u2013781 (2015).","journal-title":"Lancet Respir. Med."},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12864-016-3391-x","article-title":"Comparison of DNA quantification methodology used in the DNA extraction protocol for the UK Biobank cohort","volume":"18","author":"Welsh S.","year":"2017","unstructured":"S. Welsh, T. Peakman, S. Sheard, R. Almond, Comparison of DNA quantification methodology used in the DNA extraction protocol for the UK Biobank cohort. BMC Genomics 18, 26 (2017).","journal-title":"BMC Genomics"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach","volume":"44","author":"DeLong E. R.","year":"1988","unstructured":"E. R. DeLong, D. M. DeLong, D. L. Clarke-Pearson, Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics 44, 837\u2013845 (1988).","journal-title":"Biometrics"},{"key":"e_1_3_4_51_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1080\/01621459.1992.10475190","article-title":"Generalized collinearity diagnostics","volume":"87","author":"Fox J.","year":"1992","unstructured":"J. Fox, G. Monette, Generalized collinearity diagnostics. J. Am. Stat. Assoc. 87, 178\u2013183 (1992).","journal-title":"J. Am. Stat. Assoc."},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/qjmed\/89.10.737","article-title":"Genetics of coeliac disease","volume":"89","author":"Houlston R. S.","year":"1996","unstructured":"R. S. Houlston, D. Ford, Genetics of coeliac disease. QJM 89, 737\u2013743 (1996).","journal-title":"QJM"},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/ng.993","article-title":"Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk","volume":"44","author":"Broderick P.","year":"2011","unstructured":"P. Broderick ., Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk. Nat. Genet. 44, 58\u201361 (2011).","journal-title":"Nat. Genet."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1919976117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1919976117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T17:09:30Z","timestamp":1654621770000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1919976117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,4]]},"references-count":53,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,3,17]]}},"alternative-id":["10.1073\/pnas.1919976117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1919976117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,4]]},"assertion":[{"value":"2020-03-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}