There has been a lot of discussion on rare variants (loosely defined as <1% population frequency) and its effect on complex traits in the genetics literature lately. A new paradigm that a lot of labs are pursuing at the moment with their favorite traits is to use NGS to identify novel variants and then take these variants on a genotyping ride with larger cohorts. Because we have less statistical power with rare variants there are a lot of different approaches proposed to aggregate variants for association analysis (as opposed to the GWAS-type analysis). These methods were nicely reviewed here:
So I have gone through the hurdle of sequencing a collection of samples on a region of the genome, selecting variants for genotyping, designing a custom array and genotyped my collection of samples. Now I want to look for rare variant association. The review above contains references to a beautiful collection of methods and approaches so I contacted many of the authors of these methods to ask if they could share their code with me to analyze my data. Well... sorry to say that not many replies I received... So before I start coding away these methods my questions are:
If you have analyzed rare variants, can you recommend me a tool/approach?
Are you aware of any comparison between these approaches?