Genome-Wide Genotype Resource and Exploratory Association Analysis of Alzheimer’s Disease in a Kazakh Population: A Case–Control Study

Background/Objectives: Alzheimer’s disease (AD) has a substantial genetic component, yet Central Asian populations remain markedly underrepresented in genomic studies of the disease. Methods: to address this gap, we generated array-based genotype data using an immune-focused genotyping platform from a Kazakh AD case–control cohort and performed an exploratory association analysis. Following quality control, 180 individuals of Kazakh ancestry, including 92 individuals with AD and 88 cognitively normal controls, were analyzed. Population structure was assessed using principal component analysis, and association testing was performed using covariate-adjusted logistic regression under an additive model (primary analysis), with case–control tests under several genetic models as secondary analyses. Results: no variant reached study-wide significance; however, several exploratory association signals (p < 1 × 10−4) were identified, including variants on chromosome 9p24 and in ADARB2, MAST4, and ADAM23, which remained nominally associated after adjustment for sex, age, and principal components. In addition, APOE ε4 carrier status was evaluated in cases and controls. The proportion of APOE ε4 carriers was numerically higher among individuals with AD than among controls (40.7% vs. 26.6%), although the difference did not reach statistical significance (p = 0.074). These findings should be considered hypothesis-generating and require replication in larger independent cohorts. Conclusions: this study provides one of the first immune-focused array-based genotype datasets for AD in a Central Asian population. The publicly available genotype data and association results provide a foundation for future replication, meta-analysis, and comparative population-genetic studies of AD across diverse ancestry groups.