rs363717

A genetic association study of 1,567 Swedish dementia cases (including 1,275 with Alzheimer disease) and 2,203 controls identified variants in the ABCA1 gene associated with dementia risk. The strongest association was at rs2230805 (OR = 1.39; 95% CI 1.23-1.57; P = 7.7 × 10⁻⁸), a synonymous variant in exon 5 that was also associated with reduced cerebrospinal fluid β-amyloid-42 levels. Two distinct linkage disequilibrium blocks with signals near the ABCA1 promoter and terminal exon were identified, supporting the involvement of lipid transport genes in neurodegeneration.

This methodological study evaluates the impact of SNP marker density and linkage disequilibrium on Type I error rates and power in nonparametric multipoint linkage analysis using real genome-wide SNP data from 938 individuals in 102 COGA families. Testing five SNP densities (0.25-2 cM) with six different pedigree structures and missing data patterns, the authors found that very dense 0.25 cM maps inflated Type I error rates, particularly with missing parental genotypes and sibpair structures, while 0.3-2 cM spacing maintained appropriate error rates. The study recommends using SNP markers spaced at least 0.3 cM apart to balance informativeness with control of false positive linkage peaks.