Long-telomeropathy is associated with tumor predisposition syndrome.

Patrick Allaire, John Mayer, Luke Moat, Rachel Gabor, Jerry W Shay, Jing He, Chenjie Zeng, Lisa Bastarache, Scott Hebbring
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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 (PRS TL ) was developed. A phenome-wide association study (PheWAS) identified 65 tumor traits linked to elevated PRS TL . Using this result, a trans-ancestry phenotype risk score for a long-TL (PheRS LTL ) was develop and validated. Rare variant analyses revealed 13 genes associated with PheRS LTL . 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.

长端粒病与肿瘤易感综合征有关。
端粒保护染色体的完整性,端粒长度受环境和遗传因素的影响。虽然短端粒与罕见的端粒病有关,但这项研究探索了“长端粒病”与癌症易感综合征有关的假设。利用来自113,861个人的基因组和健康数据,开发了TL的跨祖先多基因风险评分(PRS TL)。一项全现象关联研究(PheWAS)确定了65个与PRS TL升高相关的肿瘤特征。利用这一结果,开发并验证了长tl (PheRS LTL)的跨祖先表型风险评分。罕见变异分析显示13个基因与PheRS LTL相关。携带这些罕见变异的个体具有长tl的倾向,证实了最初的假设。这些基因中的大多数对癌症和端粒生物学都是新的。总之,这项研究确定了一种由常见和罕见遗传变异形成的新型肿瘤易感综合征,将对端粒病的理解扩大到那些易患长端粒的人。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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