Nature Genetics | Free Association

Community consensus criteria

A group of researchers funded by the NIH Post-GWAS Initiative have produced a draft standards document for the cancer genomics field entitled “Principles for the post-GWAS functional characterisation of risk loci” that can be found in preprint form at Nature Precedings archive. This document is intended for publication as a Perspective in Nature Genetics. Because field-specific criteria supported by broad consensus are more likely to be useful, we have decided to invite all stakeholders to become co-authors or peer referees of this document in place of editorially supervised peer review. This is very much an experiment, some editorial judgment may be needed, or formal expert review may or may not be needed in this case.

Background on the journal’s involvement in developing field-specific standards by soliciting community consensus can be found in two Editorials, “Discussing Standards” and “On beyond GWAS”.

To become a contributor you have several options:

1) Comment using the Nature Precedings comment function.

2) Email your comments and text to the corresponding authors at snpfunction(at) whether or not you want to be considered for co-authorship.

3) Post your comments to the Nature Genetics blog freeassociation(at) letting the moderator know whether you want your comments to be attributed to you or anonymous.

4) Although our aim is consensus, substantial distinct and dissenting perspectives may need to be submitted as preprints to Nature Precedings. These can be combined into a themed Collection of preprints that will not preclude their eventual publication in journals, for example as Correspondence.

Substantial conceptual contributions and substantial contributions to the writing of the submitted document will be acknowledged with authorship in the final document if submitted before the community review deadline, December 20th 2010. If you wish to contribute to the document as a referee only, you may stipulate that you do not want co-authorship.


  1. Report this comment

    William R. Otto said:

    Dear Sir,

    I write to comment in a general way in response to an article on Wikigenes by Robert Hoffmann1 and the invitation to contribute to a paper by Monteiro and coworkers on functional genome-wide association studies2. The thoughtful and provocative article on Wikigenes is excellent in many respects, being fully in favour of a collaborative, mutualistic approach to knowledge and its use [for those afraid of the “S” word], and the [unedited] paper by Montiero and colleagues is enlightening. There are some potential conflicts at the heart of one’s ability to extend such articles. One reason this may be inhibited is that authors tend to respect other authors’ work, even in disagreement, and they would be embarassed to alter, or even correct obvious errors, in their own name unless this were in the form of a critique in their own article. This process has been the model for decades, of course, and may not be necessarily optimal in a Wikigene context. However, who would want, or dare, to alter the Watson and Crick paper on solving the structure of DNA in the light of post hoc data? Few, I suggest. That their data should be freely available to all is beyond doubt true [hurry up all you journals with your unavailable, unused, back-catalogues gathering dust]. This impinges on a central problem with a free-for-all authorship model of a “single” print or Wikigene article that may begin life as a short solo effort, but could end up with, say, a hundred authors contributing screeds of opinions, some of whom may differ widely in their views, and none of which may even be “correct” by a given hypothesis. The loudest ego is not always the wisest.

    Group activity in the Wiki world will be hopefully more kind in this respect, and I applaud this initiative, and I hope there will be room for alternative yet simultaneous views. We can all cite articles where the primary authors misinterpret their own data, and many more where one interpretation is overtaken by new knowledge. This should be how Science progresses, where individual, credibly refereed, efforts are “rewarded” by authorship, and hence grants, the sine qua non of much academic and university life today.

    However, will the Research Councils reward authors writing Wiki hypotheses and articles with grant money? With textual tracking it should be clear whose idea it was, but hijacking is a potential problem, and posted ideas may quickly result in new experiments by others which would surely deter the act itself. I have no personal problem with positing ideas there, being a generous soul. However, others will disagree, and many a patent could be lost this way, unless we devise new protections for such ideas, if we agree that such methods should be used at all. A further problem with editable authorship would be who gets the brownie points, and how many? We will need to devise new metrics for such efforts, which clearly deserve rewards. As for this minor effort, I guess I get the brownie points till somebody disagrees with my text and amends it. What then? One hopes database servers will be large enough to hold historical versions which can live on as an interactive archive, so that original efforts can be reinterpreted with and without later data. There could be useful progress in that too. The Wikigenes world will no doubt be very useful in this context.

    Yours faithfully,

    William R Otto PhD


    1 Hoffmann R Nature Genetics 40, 1047 – 1051 (2008) A wiki for the life sciences where authorship matters. Published online: 27 August 2008 | doi:10.1038/ng.f.217.

    2 Monteiro ANA et al Nature Genetics (2010) Principles for the post-GWAS functional characterisation of risk loci.

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    gioby said:

    This is a very nice initiative, personally I am taking it as a nice exercise. A good researcher should be able to read critically a paper written by someone else, and identify what can be improved and what can be added; this is a good opportunity to talk to the authors of an article before it is published, and verify whether the changes one would made are correct or not.

    However, if you want many people to participate effectively, you should explain better what is the article about. People should be able to decide whether they can make good contributions without having to read the whole draft first; this is because a lot of potential contributors do not have the time to read it carefully and give up before knowing what the article is about.

    Personally, I think that the draft lacks a chapter on computational functional characterization of the variants identified; I am making some contributions to the wiki, and I am thinking about involving the community into this.

  3. Report this comment

    Xuejun Zhang said:

    Dear sir:

    I am herein make a comment in a general way in response to the article by Monteiro and colleagues on “Principles for the post-GWAS functional characterisation of risk loci” and the invition to contribute to it1. It is ture that the vast majority disease associated SNPs including cancer related SNPs identified by GWAS are only markers of putative risk and are not necessarily the functional genetic variants themselves. Finding these variants, investigating their functional characterisation and linking them to causation is essential for understanding the biological processes underlying disease pathogenes, which is ultimate goal for any disease. The thoughtful and provocative paper by Monteiro and coworkers is very nice enlightening and initiative, although some ideas are speculative by some given hypotheses as well as there will be room for alternative opinions and even some of them will be overtaken by new knowledge.

    They set up a general frame in terms of outlining a hierarchical approach for functional study on post-GWAS in the context of current technologies and knowledge, personally I think it is a nice try in many respects such as reinterpreting and delimiting the LD structure boundaries, investigating the transcriptional effects of SNPs in gene-distal or –proximal regions by epigenetics and exploring the functions of SNP in regulatory sequences/regions. This should be research exploration and how Sciense progresses. However, most effect sizes of the susceptibility SNPs are small relative with per allele odds ratios usually ranging from 1.15 to 1.3 and thus the functional effects of SNPs are likely to be subtle1. Furthermore, functional studies both in vitro and vivo experiments are time-consuming and challenging. In order to optimize the allocation of effort and resources and maximize the chances of elucidating the functional contribution of specific loci to the disease phenotype, I suggest that they should add a charpter on computational functional characterization of the disease associated SNPs in terms of screening the potential causual variants and predicting their function before performing some functional studies on target SNPs or genes both in vitro and vivo experiments. The combination using of multiple disciplines such as bioinformatics, mathematics, biostatistics and computer sciense will faciliate it. Definitely, Monteiro and colleagues make the first important step on the functional characterization of SNPs in post-GWAS era, which will help bridge the information gap for assigning functionality to susceptibility SNPs, identify causal variants and eventually elucidate the pathogenesis of complex disease. I am happy to become a co-author or peer referee of this document according to the editorial and the authors’s judgment.

    With best wishes

    Your sincerely: Xue-Jun Zhang M.D Ph.D

    Add:81,Meishan Road,Hefei city,Anhui province,China.230032


    1.Monteiro ANA et al Nature Genetics (2010) Principles for the post-GWAS functional characterisation of risk loci.