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Long-telomeropathy is associated with tumor predisposition syndrome

Allaire, P.; Mayer, J.; Moat, L.; Gabor, R.; Shay, J.; He, J.; Zeng, C.; Bastarache, L.; Hebbring, S.

2024-11-28 genetic and genomic medicine
10.1101/2024.11.26.24318007 medRxiv
Show abstract

Telomeres protect chromosomal integrity, and telomere length (TL) is influenced by environmental and genetic factors. While short-telomeres are linked to rare telomeropathies, this study explored the hypothesis that a "long-telomeropathy" is associated with a cancer-predisposing syndrome. Using genomic and health data from 113,861 individuals, a trans-ancestry polygenic risk score for TL (PRSTL) was developed. A phenome-wide association study (PheWAS) identified 65 tumor traits linked to elevated PRSTL. Using this result, a trans-ancestry phenotype risk score for a long-TL (PheRSLTL) was develop and validated. Rare variant analyses revealed 13 genes associated with PheRSLTL. Individuals who were carriers of these rare variants had a predisposition for long-TL validating original hypothesis. Most of these genes were new to both cancer and telomere biology. In conclusion, this study identified a novel tumor-predisposing syndrome shaped by both common and rare genetic variants, broadening the understanding of telomeropathies to those with a predisposition for long telomeres.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.