Assessing thyroid cancer risk using polygenic risk scores

Proceedings of the National Academy of Sciences of the United States of America
Sandya LiyanarachchiAlbert de la Chapelle

Abstract

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) com...Continue Reading

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Citations

May 27, 2020·Médecine sciences : M/S·Bertrand Jordan
Nov 12, 2020·The Journal of Clinical Endocrinology and Metabolism·Marco CapezzoneMaria Grazia Castagna
Feb 23, 2021·Human Molecular Genetics·Xiaopeng XuYong-Biao Zhang
Mar 20, 2021·The Journal of Clinical Endocrinology and Metabolism·Carl D Malchoff
Sep 2, 2021·Annual Review of Biomedical Data Science·Nicola MulderYasmina Jaufeerally Fakim
Sep 2, 2021·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Nan SongZhaoming Wang

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