Has anybody tested if paralogous genes are over-represented among the genes identified by genome-wide association studies (GWAS)?

For example, if a GWAS study finds 200 genes associated to the disease/trait, and a number X of those can be classified as belonging to Y different gene families, is there a test to see if X and Y are bigger than expected, given the total number of genes and gene paralogies in a genome? Here I am talking long established copies within a species, not CNVs in different individuals of the same species.

I am thinking there is an interesting question behind this: if a gene has duplicated during the evolution of a genome, and the different gene copies have taken specialized, yet related, roles, an unbiased analysis like GWAS should be able to find cases where different paralogous copies associate to different subdiseases/subtraits within the same global disease/trait.

  • $\begingroup$ Hello. Could you help by clarifying your question? Do you want to know whether paralogous genes/regions are over-represented in GWAS hits? It is an interesting hypothesis - have you any ideas/references why this may be the case? It's always best to give as full and clear a question as possible. Thanks $\endgroup$
    – Luke
    Jul 3, 2012 at 14:25
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    $\begingroup$ That is an interesting question (thanks for the expansion). If the paralogous genes were still functionally related there is likely to be redundancy between them, so a SNP in one of the copies may not manifest at all. A SNP that affects a sub-trait specific to one of the copies would need to have a massive effect (or the study would require a phenomonal sample size) to find it (unless it was a targeted study only on paralogous genes known to be disease related?). I don't know fo any studies, but will be interested in others answers! $\endgroup$
    – Luke
    Jul 3, 2012 at 15:19
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    $\begingroup$ Is a Fisher's exact test (a chi-squared test with more relaxed assumptions) something you've considered? $\endgroup$
    – Atticus29
    Feb 5, 2013 at 8:41
  • $\begingroup$ I actually don't understand what the hypothesis is. First, there are tons of confounding factors to control for -- for instance, regulatory gene families may be more likely to expand than structural gene families, so you'd need to account for that (and a lot more). Your final question regarding subfunctionalization seems to have nothing to do with the original question of over-representation. $\endgroup$
    – adam.r
    Dec 1, 2013 at 19:41
  • $\begingroup$ Aren't paralogs supposed to have divergent function? I would expect them to be under-represented. $\endgroup$
    – Superbest
    Apr 3, 2014 at 2:43

1 Answer 1


There is no literature report saying such a thing. However, I did a cursory check for GWAS study on neuroblastoma.

  • Selected SNPs with p-value>0.05
  • Converted p-values to a score —
  • Mapped the SNPs to genes while calculating cumulative score for a gene

I just sorted the genes based on their names, assuming that many paralogs have similar names. I know it is not the right way to go about it. However, I found many similar named groups in the list.

Now the next step is find actual paralogs and to score the cumulative score for a paralog-group. This is a little task:

  • Get sequences of the genes
  • Run a BLAST search to find paralogs
  • Assign genes to groups and find scores

I can share the file with genes and scores. I would, however, continue only if someone is actually interested in pursuing this — this could be a research paper.

PS: If you want the file just comment your email id. Some IT admin idiot has blocked rapidshare/4shared etc


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