IKZF1的非编码调控变体会增加西班牙裔/拉美裔儿童患急性淋巴细胞白血病的风险。

IF 11.1 Q1 CELL BIOLOGY
Cell genomics Pub Date : 2024-04-10 Epub Date: 2024-03-26 DOI:10.1016/j.xgen.2024.100526
Adam J de Smith, Lara Wahlster, Soyoung Jeon, Linda Kachuri, Susan Black, Jalen Langie, Liam D Cato, Nathan Nakatsuka, Tsz-Fung Chan, Guangze Xia, Soumyaa Mazumder, Wenjian Yang, Steven Gazal, Celeste Eng, Donglei Hu, Esteban González Burchard, Elad Ziv, Catherine Metayer, Nicholas Mancuso, Jun J Yang, Xiaomei Ma, Joseph L Wiemels, Fulong Yu, Charleston W K Chiang, Vijay G Sankaran
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引用次数: 0

摘要

在美国,与其他种族/族裔群体相比,西班牙裔/拉美裔儿童罹患急性淋巴细胞白血病(ALL)的风险最高,但人们对这一现象的基础仍不甚了解。通过基因精细图谱分析,我们在自我报告的西班牙裔/拉美裔个体中发现了IKZF1附近的一个新的独立儿童ALL风险信号,但在非西班牙裔白人个体中却没有发现该信号,其效应大小为∼1.44(95% 置信区间 = 1.33-1.55),在西班牙裔/拉美裔人群中的风险等位基因频率为∼18%,而在非西班牙裔/拉美裔人群中的风险等位基因频率为∼20%。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.

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