小柯机器人

美国贝勒医学院Christopher I. Amos团队近期取得重要工作进展，他们通过对61,047个病例和947237例对照的跨祖先全基因组荟萃分析发现了新的肺癌易感位点。该项研究2022年8月1日在线发表于《自然—遗传学》杂志上。

为了在不同人群中确定新的肺癌易感位点，研究人员在欧洲、东亚和非洲人群中进行了跨血统全基因组关联研究，发现了五个以前未报道过的位点。他们复制了26个信号，并从先前报告的基因座中确定了10个新的先导关联。稀有变异关联往往倾向于特定人群，但即使是影响吸烟行为的常见变异关联，例如CHRNA5和CYP2A6的关联，也显示出人群特异性。

精细定位和表达数量性状基因座共定位提名了几个候选变体和易感基因，如IRF4和FUBP1。 肺成纤维细胞中优先基因的DNA损伤分析表明，这些基因的一个子集，包括多效基因IRF4，可能通过促进内源性DNA损伤发挥作用。

附：英文原文

Title: Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer

Author: Byun, Jinyoung, Han, Younghun, Li, Yafang, Xia, Jun, Long, Erping, Choi, Jiyeon, Xiao, Xiangjun, Zhu, Meng, Zhou, Wen, Sun, Ryan, Boss, Yohan, Song, Zhuoyi, Schwartz, Ann, Lusk, Christine, Rafnar, Thorunn, Stefansson, Kari, Zhang, Tongwu, Zhao, Wei, Pettit, Rowland W., Liu, Yanhong, Li, Xihao, Zhou, Hufeng, Walsh, Kyle M., Gorlov, Ivan, Gorlova, Olga, Zhu, Dakai, Rosenberg, Susan M., Pinney, Susan, Bailey-Wilson, Joan E., Mandal, Diptasri, de Andrade, Mariza, Gaba, Colette, Willey, James C., You, Ming, Anderson, Marshall, Wiencke, John K., Albanes, Demetrius, Lam, Stephan, Tardon, Adonina, Chen, Chu, Goodman, Gary, Bojeson, Stig, Brenner, Hermann, Landi, Maria Teresa, Chanock, Stephen J., Johansson, Mattias, Muley, Thomas, Risch, Angela, Wichmann, H.-Erich, Bickebller, Heike, Christiani, David C., Rennert, Gad, Arnold, Susanne, Field, John K., Shete, Sanjay, Le Marchand, Loic, Melander, Olle, Brunnstrom, Hans, Liu, Geoffrey, Andrew, Angeline S., Kiemeney, Lambertus A., Shen, Hongbing, Zienolddiny, Shanbeh, Grankvist, Kjell

Issue&Volume: 2022-08-01

Abstract: To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage. A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk.

DOI: 10.1038/s41588-022-01115-x

Source: https://www.nature.com/articles/s41588-022-01115-x

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