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This study provides a new version of the arrayed primer extension (APEX) protocol adapted to the ‘array of arrays’ platform using an instrumental setup for microarray processing not previously described. The primary aim of the study is to implement a system for rational cost-efficient genotyping where multiple singlenucleotide polymorphisms (SNPs) and individuals are genotyped on each microarray slide. Genotyping results are collected across 185 healthy Danish subjects and 76 SNPs on chromosome 3q13.31, because linkage to atopic disease phenotypes have been suggested in the Danish population. Linkage disequilibrium (LD) results from the experimental data are used in a novel comparison to baseline data defined by the international HapMap SNP database. Comparison on the LD results reveals a strong linear correlation irrespective of LD measure considered R2(D′) 0.73 and R2(r2) 0.54. In conclusion, our results show that this setup is strong enough to support high-throughput genotyping, and these observations support that the HapMap genotype resource is important for defining SNP panels aimed at gene mapping in local subpopulations from Europe. [ABSTRACT FROM AUTHOR]

The efficiency of the popular case-control design in gene-longevity association studies needs to be verified because, different from a binary trait, longevity represents only the extreme end of the continuous life span distribution without a clear cutoff for defining the phenotype. In this paper, the authors use the current Danish life tables to simulate individual life span by using a variety of scenarios and assess the empirical power for different sample sizes when cases are defined as centenarians or as nonagenarians. Results show that, although using small samples of centenarians (several hundred) provides power to detect only common alleles with large effects (a >20% reduction in hazard rate), large samples of centenarians (>1,000) achieve power to capture genes responsible for minor effects (5%–10% hazard reduction depending on the mode of inheritance). Although the method provides good power for rare alleles with multiplicative or dominant effects, it performs poorly for rare recessive alleles. Power is drastically reduced when nonagenarians are considered cases, with a more than 5-fold difference in the size of the case sample required to achieve comparable power as that found with centenarians. [ABSTRACT FROM AUTHOR]