Rationale For Different Types Of Snp--> Gene Mapping For Pathway Analysis

Question

[Joey]

Is there a reference one can point me to which speaks about the different ways one can map SNP--> Genes for pathway analysis?

There seems to be many ways one can map SNP to genes: 500kb upstream and downstream of gene; 100kb upstream and downstream of gene; 20kb upstream and downstream of gene; 5kb upstream and downstream of gene; within gene; functional SNP (nonsynonymous, stop gained/lost, frame shift, essential splice site, regulatory region) . I found this on the i-Gsea4Gwas website but it doesn't say anything about use cases. One tends to get different answers in terms of top pathways with different mapping schemes. And I'm guessing that the rationale for choosing one of the scheme might also differ depending on the type of data one is using (say..just observed SNPs vs. 1000G imputed SNPS etc.).

Thanks,

-Joey

Answer 1

[Istvan Albert]

The rationale is that various parts of the genome can have many different functions and may participate in regulation in various direct and indirect ways.

It is not uncommon to see one snp, one phenotype style of of expectations - understandably so, who wouldn't want to be able to explain a phenotype via a single well defined snp. Alas in the vast majority of cases the reality is a complex mesh of overlapping pathways and regulations that manifest themselves differently over different distances and contexts.

Of course then we are left asking - so where does one start, which one is right. To which there is no single well defined answer. That's what scientific investigation is about.