Power of selective genotyping in genome-wide association studies of quantitative traits.

The selective genotyping approach in quantitative genetics means genotyping only individuals with extreme phenotypes. This approach is considered an efficient way to perform gene mapping, and can be applied in both linkage and association studies. Selective genotyping in association mapping of quantitative trait loci was proposed to increase the power of detecting rare alleles of large effect. However, using this approach, only common variants have been detected. Studies on selective genotyping have been limited to single-locus scenarios. In this study we aim to investigate the power of selective genotyping in a genome-wide association study scenario, and we specifically study the impact of minor allele frequency of variants on the power of this approach. We use the Genetic Analysis Workshop 16 rheumatoid arthritis whole-genome data from the North American Rheumatoid Arthritis Consortium. Two quantitative traits, anti-cyclic citrullinated peptide and rheumatoid factor immunoglobulin M, and one binary trait, rheumatoid arthritis affection status, are used in the analysis. The power of selective genotyping is explored as a function of three parameters: sampling proportion, minor allele frequency of single-nucleotide polymorphism, and test level. The results show that the selective genotyping approach is more efficient in detecting common variants than detecting rare variants, and it is efficient only when the level of declaring significance is not stringent. In summary, the selective genotyping approach is most suitable for detecting common variants in candidate gene-based studies.