Here, we re-examine TOMM40-523' as a race/ethnicity-specific risk modifier for late-onset Alzheimer disease (LOAD) with adjustment for local genomic ancestry (LGA) in Apolipoprotein E (APOE) 4 haplotypes.

The TOMM40-523' size was determined by fragment analysis and whole genome sequencing in homozygous APOE 3 and APOE 4 haplotypes of African (AF) or European (EUR) ancestry. The risk for LOAD was assessed within groups by allele size.

The TOMM40-523' length did not modify risk for LOAD in APOE 4 haplotypes with EUR or AF LGA. Increasing length of TOMM40-523' was associated with a significantly reduced risk for LOAD in EUR APOE 3 haplotypes.

Adjustment for LGA confirms that TOMM40-523' cannot explain the strong differential risk for LOAD between APOE 4 with EUR and AF LGA. Our study does confirm previous reports that increasing allele length of the TOMM40-523' repeat is associated with decreased risk for LOAD in carriers of homozygous APOE 3 alleles and demonstrates that this effect is occurring in those individuals with the EUR LGA APOE 3 allele haplotype.

在这里，我们重新检查TOMM40 -523' 作为晚发性阿尔茨海默病 (LOAD) 的种族/民族特异性风险修饰剂，并对载脂蛋白 E ( APOE) 4 单倍型中的局部基因组祖先 (LGA) 进行调整。

TOMM40 -523' 大小是通过非洲 (AF) 或欧洲 (EUR) 血统的纯合APOE 3 和APOE 4 单倍型的片段分析和全基因组测序确定的。根据等位基因大小在组内评估 LOAD 的风险。

TOMM40 -523' 长度不会改变具有 EUR 或 AF LGA 的APOE 4单倍型中的 LOAD 风险。 TOMM40 -523' 长度的增加与 EUR APOE 3 单倍型中 LOAD 风险的显着降低相关。

LGA 的调整证实TOMM40 -523' 无法解释APOE 4 与 EUR 和 AF LGA 之间 LOAD 的强烈差异风险。我们的研究确实证实了之前的报道，即增加TOMM40-523'重复的等位基因长度与纯合APOE 3 等位基因携带者的 LOAD 风险降低相关，并证明这种效应发生在具有 EUR LGA APOE 3 等位基因单倍型的个体中。