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Polygenic Traits01:18

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When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...
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Calcium-Scoring CT ScanA calcium-scoring CT scan, also known as coronary artery calcium (CAC) scan, detects calcium deposits in the coronary arteries. This test assesses the risk of coronary artery disease (CAD), which can lead to cardiovascular events such as angina, heart failure, and sudden cardiac arrest.A calcium-scoring CT scan is generally recommended for individuals at intermediate risk of CAD without symptoms. It includes:Men aged 40-75 and women aged 50-75: Especially those with a...
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Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
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Genome-wide Association Studies-GWAS01:11

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Assessing thyroid cancer risk using polygenic risk scores.

Sandya Liyanarachchi1,2, Julius Gudmundsson3, Egil Ferkingstad3

  • 1Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.

Proceedings of the National Academy of Sciences of the United States of America
|March 6, 2020
PubMed
Summary

A polygenic risk score (PRS) using 10 common genetic variants significantly improves papillary thyroid cancer (PTC) risk prediction. This highlights the importance of heritable, low-penetrance markers in PTC susceptibility.

Keywords:
GWASpolygenic risk scorerisk predictionthyroid cancer

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Area of Science:

  • Genetics
  • Cancer Epidemiology
  • Genomic Risk Prediction

Background:

  • Genome-wide association studies (GWASs) have identified numerous single-nucleotide polymorphisms (SNPs) linked to papillary thyroid cancer (PTC) risk.
  • These identified SNPs are predominantly common variants with small to moderate effect sizes.

Purpose of the Study:

  • To evaluate the combined genetic effects of established PTC-associated SNPs on cancer risk.
  • To develop and validate polygenic risk score (PRS) models for predicting PTC susceptibility.

Main Methods:

  • Utilized summarized GWAS results to construct PRS models across three independent PTC study cohorts (Ohio, Iceland, UK).
  • Compared the predictive performance of a 10-SNP PRS against a clinical factors model and an extended PRS incorporating over 592,000 common variants.

Main Results:

  • The 10-SNP PRS demonstrated significantly enhanced predictive power for PTC risk compared to clinical factors alone (minimum AUC increase of 5.4%, P ≤ 1.0 × 10⁻⁹).
  • Incorporating a larger set of common variants (592,475) did not substantially improve prediction, suggesting rare variants may contribute more to undiscovered genetic risk.
  • Individuals in the top PRS decile exhibited a nearly sevenfold increased risk of PTC compared to those in the bottom decile.

Conclusions:

  • PRS models based on a limited number of common germline variants effectively predict PTC risk.
  • The findings underscore the significant contribution of heritable, low-penetrance genetic markers to papillary thyroid cancer susceptibility.