Why GWASs cannot speculate what kind of mutation the SNP would cause?

Question

[francois]

I am trying to understand results from GWAS studies, and I have this question:

Why can't GWAS studies speculate about what kind of consequence would the specific SNP have? As they information about the precise position on the genome + which base changes, I thought studies would speculate if the SNP in question causes a silent/missense/nonsense mutation, but they apparently do not (at least those I have read).

I guess some information is missing or uncertain to speculate about that... What is it? I was thinking maybe which frame is read?

Any guess?

Answer 1

[Noushin N]

Adding to the response by swbarnes2, many of the variants identified in GWAS are located in non-coding regions of the genome and will function not by altering the protein coding sequences, but by regulation of gene expression.

[Collin]

My assumption is that generally the "lead" SNPs identified as most significant in GWAS are not necessarily the actual causal SNP because of linkage disequilibrium. Therefore trying to ascertain a function or effect of those SNPs would be misleading. I believe they generally try to do further studies on implicated loci (called "fine-mapping") to more precisely locate the likely causal variants (e.g., pmid: 26551672).

[Noushin N]

Great point! Thanks for the addition, Collin!

Answer 2

[swbarnes2]

It's easy to predict the amino acid change consequence of a mutation. What's hard is to predict the functional consequences of most changes.