I'm trying to analyze data from a genotype-phenotype association study. The genotype data is stored in csv files that record for each variant site and each subject, the alleles that the subject has at that site. A quick online search reveals that 0 means the reference allele, 1 means the most common alternate allele, 2 means the 2nd most common alternate allele, etc.
But I noticed that at some variant sites, most (>90%) subjects have 1/1, i.e. two copies of the alternate allele. I asked around and some suggested I just swap the roles of reference and alternate alleles whenever I find that the alternate allele frequency > 0.5. My questions are:
- Can there be a good reason to classify a less common allele as the reference allele? I thought that the reference allele was defined as the most common one in the population.
- Is swapping the roles of reference and alternate alleles whenever I find that the alternate allele frequency > 0.5 a standard practice?