文章：

全外显子组关联分析揭示GALNT9罕见变异与中东地区乳头状甲状腺癌风险相关

Whole Exome-Wide Association Identifies Rare Variants inGALNT9Associated with Middle Eastern Papillary Thyroid Carcinoma Risk

原文发布日期：24 August 2023

DOI: 10.3390/cancers15174235

类型: Article

开放获取: 是

英文摘要：

Papillary thyroid carcinoma (PTC) is the commonest thyroid cancer. The majority of inherited causes of PTC remain elusive. However, understanding the genetic underpinnings and origins remains a challenging endeavor. An exome-wide association study was performed to identify rare germline variants in coding regions associated with PTC risk in the Middle Eastern population. By analyzing exome-sequencing data from 249 PTC patients (cases) and 1395 individuals without any known cancer (controls),GALNT9emerged as being strongly associated with rare inactivating variants (RIVs) (4/249 cases vs. 1/1395 controls, OR = 22.75,p= 5.09 × 10−5). Furthermore, three genes,TRIM40,ARHGAP23, andSOX4, were enriched for rare damaging variants (RDVs) at the exome-wide threshold (p< 2.5 × 10−6). An additional seven genes (VARS1,ZBED9,PRRC2A,VWA7,TRIM31,TRIM40, andCOL8A2)were associated with a Middle Eastern PTC risk based on the sequence kernel association test (SKAT). This study underscores the potential ofGALNT9and other implicated genes in PTC predisposition, illuminating the need for large collaborations and innovative approaches to understand the genetic heterogeneity of PTC predisposition.

摘要翻译： 

甲状腺乳头状癌（PTC）是最常见的甲状腺癌类型。其遗传性病因大多尚未明确，理解其遗传基础与起源仍具挑战性。本研究通过全外显子组关联分析，旨在识别中东人群中与PTC风险相关的编码区罕见种系变异。通过分析249例PTC患者（病例组）和1395名无已知癌症个体（对照组）的外显子组测序数据，发现GALNT9基因与罕见失活变异（RIVs）显著相关（病例组4/249 vs. 对照组1/1395，OR = 22.75，p = 5.09 × 10−5）。此外，TRIM40、ARHGAP23和SOX4三个基因在全外显子组显著性阈值（p < 2.5 × 10−6）下呈现罕见有害变异（RDVs）富集。基于序列核关联检验（SKAT），另有七个基因（VARS1、ZBED9、PRRC2A、VWA7、TRIM31、TRIM40和COL8A2）与中东人群PTC风险相关。本研究揭示了GALNT9及其他相关基因在PTC遗传易感性中的潜在作用，强调需要通过大规模合作与创新方法以解析PTC遗传易感性的异质性。

原文链接：

Whole Exome-Wide Association Identifies Rare Variants inGALNT9Associated with Middle Eastern Papillary Thyroid Carcinoma Risk