Horimoto, Boyken, Blue, et al. (2023) Admixture mapping implicates 13q33.3 as ancestry-of-origin locus for Alzheimer disease in Hispanic and Latino populations. HGG Advances, 4, 100207. PMCID: PMC10276158.
Admixed populations descended from multiple ancestral populations are under-represented in genetic studies of disease while the studies that are available are limited by small sample sizes and analytical challenges. To address those challenges, we developed and validated a logistic mixed model for admixture mapping with binary traits named LLAMA and implemented it in the GENESIS bioconductor package. We applied our approach to find loci associated with Alzheimer’s disease (AD) risk among multiplex Caribbean Hispanic families as part of the , identifying three loci on 13q33.3 associated with reduced risk of AD for those with Native American haplotype.Independent replication analyses of data from the consortium support this association, but traditional genome-wide association study (GWAS) methods failed to replicate the signal even within the ADSP data. This study is important because it underscores the need for and potential of admixture mapping to identify genetic loci associated with disease. Contributing consortia:Alzheimer’s Disease Sequencing Project (ADSP), Alzheimer’s Genetics in Argentina—Alzheimer Argentina