Association Study of Rare Variants and Disease in Case-Parental Data with One of Parents Missing

In exploring the field of association between disease and genes especially in GWAS (genome-wide association studies), there were large multiple variants in data collection. These variants have MAF (minor allele frequency) with large than 5%. We wanted to detect the causal factors for certain disease in GWAS in either population-based or family-based. So far, the common disease common variant hypothesis must hold true. But, recent studies told us that the CVs have provided just a fraction of the genetic risk with most disease. There was not only a minority CVs to induce the disease. The disease affected from functional rare variants (RVs). The RVs could come from resequencing data, and their MAFs were less than 0.1%. Individuals with large number of functional RVs (or multiple RVs) have the higher risk to a complex disease. In our previous studies, we found out that the method for CVs to search for relation with disease and genes would not be suitable in multiple RVs. The type I error rate were be rise and departure from specify significant level in these methods. We already proposed the new method of employment in the RVs data in family-based with case-parental case design. It is true that we don’t consider problem for population stratification in family. Further, we would discuss the RVs related to disease when one of the parents would be missing. The idea of method comes from the comparison of the frequency of transmitted risk allele and non-transmitted risk allele. If the test could control the given type I error rate and have higher power, we would apply to genome-wide data and resequencing data in practical.