Work

Genome‐wide association meta‐analyses in Chinese and European individuals yield new insights into the etiology of Alzheimer’s disease

Year: 2024

Type: article

Abstract: BACKGROUND: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology, yet most known loci were only identified from the late-onset type of European ancestry. METHOD: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6,878 Chinese and 487,511 European individuals. RESULT: We demonstrated a shared genetic architecture between early- and late-onset AD. In addition to the APOE locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). Notably, the TCN2 locus showed genome-wide significant associations with AD in both discovery and replication stages in Chinese populations. More replicated variants were observed in the Chinese (31%) than European samples (4%). Combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might be protective against AD. CONCLUSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.084356