Nature Genetics | Free Association

Update on post-GWAS functional standards paper

It is interesting to see how new views are building up as more authors join the initiative to develop the draft standards paper. It is also fascinating to see them experiment with new tools and services for a diverse author group. There is now an active discussion page for authors and referees of the standards paper at Wikigenes. A collection of relevant supporting papers has been assembled on Mendeley. It would be great if the corresponding authors have time to submit a revised draft to Nature Precedings before the authoring deadline so that we can see how the reference copy has evolved.


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    Giovanni Dall'Olio said:

    Thank you for sponsoring the discussion page and the Mendeley group! Not everybody see them when they start editing the manuscript, so it is useful if you point to them. We have also created a discussion on the Biostar project ( and personally, I am trying to contact all the people who could be interested, like the authors of papers relevant to the topic.

    I didn’t know that the manuscript was being modified since the reference copy posted in WikiGenes, but I think it won’t be too difficult to integrate it with the version being edited collaboratively.

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    Giovanni Dall'Olio said:

    Here it is a resume on the new paragraphs/addition that have been made since the original version.

    summary: the manuscript is a perspective on approaches and good practices to study the function of a variant identified in a GWAS.

    It happens too often that, after a GWAS is successful in identifying a relationship between a tag SNP and a disease, these results are not followed by a study on the biological mechanism behind the association, or by studies on the exact location of the causal variant.

    • added references to the Uk10K project, and improved the description of 1000genomes

    • created a chapter on computational methods to predict the function of a variant. We described the databases that annotate information on SNPs or other association studies, tools like GRAIL to analyze the literature, cited the utility of genome browser like UCSC’s, cited a study where the authors have described a pipeline to predict the effect of a non-synonymous SNP on the structure of a protein (the author of the paper have been contacted and will contribute to the paper) and we will describe how to predict pseudogenes or functional elements, and a bit about pathway approaches.

    • described how alternative splicing can add complexity to eQTL association studies

    • described the complexity of using RNA-Seq and microarrays (also in table 1), plus a few details on Zinc-Finger technologies

    • described that it is important to take into account the interactions between chromatine fibres when studying the effect of a SNP. Different genotypes can be associated with a different chromatine network, which adds a whole level of complexity when predicting the effect of a SNP on the phenotype.

    • differences between studying SNPs and CNVs

    • discussed the usage of BRCA1 cancers as models to validate GWAS

    • added some motivations on why animal models are not perfect to reproduce the effect of a SNP in human