Ethnic‐specific effects of the LILRB2–LILRB5 locus and newly identified risk loci for Alzheimer's disease in the East Asian population

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.