Ethnic‐specific effects of the LILRB2–LILRB5 locus and newly identified risk loci for Alzheimer's disease in the East Asian population
Alzheimer's & Dementia, 2026
Cao H., Zheng Z., Zhou X., Kikuchi M., Wong H., Cheng E., Wong B., Lo R., Shoai M., Chong J., Chan A., Chen C., Lam L., Mok V., Kwok T., Chen Y., Ip F., Mok K., Miyashita A., Ikeuchi T., Hardy J., Fu A., Ip N.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
INTRODUCTION
Genome‐wide association studies have identified numerous Alzheimer’s disease (AD) susceptibility loci in European populations. However, the genetic architecture of AD in non‐European populations remains underinvestigated.
METHODS
We performed a genetic association study in East Asians ( N = 8514) to validate known AD loci and identify new susceptibility loci.
RESULTS
We identified LILRB2–LILRB5 as an AD susceptibility locus with ethnic‐specific effects between Europeans and East Asians. The lead variant, rs587709‐T, was associated with decreased AD risk and increased LILRB5 expression in Europeans. Conversely, in East Asians, the same allele was associated with increased AD risk and increased LILRB2 expression. Furthermore, genome‐wide analysis identified TTC3 and FAM135A as candidate susceptibility loci for AD or cognition.
DISCUSSION
The results establish LILRB2–LILRB5 as a cross‐ancestry AD‐associated locus with ethnic‐specific genetic mechanisms and reveal new susceptibility loci, extending the understanding of the genetic etiology of AD.