{Reference Type}: Journal Article
{Title}: A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.
{Author}: de Smith AJ;Wahlster L;Jeon S;Kachuri L;Black S;Langie J;Cato LD;Nakatsuka N;Chan TF;Xia G;Mazumder S;Yang W;Gazal S;Eng C;Hu D;Burchard EG;Ziv E;Metayer C;Mancuso N;Yang JJ;Ma X;Wiemels JL;Yu F;Chiang CWK;Sankaran VG;
{Journal}: Cell Genom
{Volume}: 4
{Issue}: 4
{Year}: 2024 Apr 10
暂无{DOI}: 10.1016/j.xgen.2024.100526
{Abstract}: 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.