Rare variant association analysis for exome study without controls

Question

[mkaushal]

Hello All,

I am new to rare variant association analysis for exome data. The study which I am currently working on has around 120 affected individuals but no controls. I have shortlisted variants from some genes and wanted to perform burden test/SKAT for my data. Can I use 1000 genome controls for this purpose? Can someone help me with which tool to use and the study design?

Answer 1

[Jason Chen]

It would not be ideal but if you cannot get any other exome chip data then this might be okay. Does the chip you are using include ancestry informative SNPs? I would first extract the 1000 genomes samples that match your study population. Then merge them, test for population structure (MDS plot, QQ plot, etc) and cryptic relatedness using common SNPs. After removing problematic samples and doing QC, you can try the burden test/SKAT.

PS Given the small sample size I wouldn't hold your breath to find something.