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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.

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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 –  Luke Jul 3 '12 at 14:25
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! –  Luke Jul 3 '12 at 15:19
Is a Fisher's exact test (a chi-squared test with more relaxed assumptions) something you've considered? –  Atticus29 Feb 5 '13 at 8:41
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. –  adam.r Dec 1 '13 at 19:41
Aren't paralogs supposed to have divergent function? I would expect them to be under-represented. –  Superbest Apr 3 at 2:43

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