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@ARTICLE{Brigante:182090,
author = {G. Brigante and C. Lazzaretti and E. Paradiso and F. Nuzzo
and M. Sitti and F. Tüttelmann and G. Moretti and R.
Silvestri and F. Gemignani and A. Försti$^*$ and K.
Hemminki$^*$ and R. Elisei and C. Romei and E. A. Zizzi and
M. A. Deriu and M. Simoni and S. Landi and L. Casarini},
title = {{G}enetic signature of differentiated thyroid carcinoma
susceptibility: a machine learning approach.},
journal = {European thyroid journal},
volume = {11},
number = {5},
issn = {2235-0640},
address = {Basel},
publisher = {Karger},
reportid = {DKFZ-2022-02408},
pages = {e220058},
year = {2022},
abstract = {To identify a peculiar genetic combination predisposing to
differentiated thyroid carcinoma (DTC), we selected a set of
single nucleotide polymorphisms (SNPs) associated with DTC
risk, considering polygenic risk score (PRS), Bayesian
statistics and a machine learning (ML) classifier to
describe cases and controls in three different datasets.
Dataset 1 (649 DTC, 431 controls) has been previously
genotyped in a genome-wide association study (GWAS) on
Italian DTC. Dataset 2 (234 DTC, 101 controls) and dataset 3
(404 DTC, 392 controls) were genotyped. Associations of 171
SNPs reported to predispose to DTC in candidate studies were
extracted from the GWAS of dataset 1, followed by
replication of SNPs associated with DTC risk (P < 0.05) in
dataset 2. The reliability of the identified SNPs was
confirmed by PRS and Bayesian statistics after merging the
three datasets. SNPs were used to describe the case/control
state of individuals by ML classifier. Starting from 171
SNPs associated with DTC, 15 were positive in both datasets
1 and 2. Using these markers, PRS revealed that individuals
in the fifth quintile had a seven-fold increased risk of DTC
than those in the first. Bayesian inference confirmed that
the selected 15 SNPs differentiate cases from controls.
Results were corroborated by ML, finding a maximum AUC of
about 0.7. A restricted selection of only 15 DTC-associated
SNPs is able to describe the inner genetic structure of
Italian individuals, and ML allows a fair prediction of case
or control status based solely on the individual genetic
background.},
keywords = {differentiated thyroid cancer (Other) / machine learning
(Other) / single nucleotide polymorphism (Other)},
cin = {B062 / HD01 / C020},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)C020-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35976137},
pmc = {pmc:PMC9513665},
doi = {10.1530/ETJ-22-0058},
url = {https://inrepo02.dkfz.de/record/182090},
}