This analysis of 845 papers from the NHGRI catalog of GWAS identified 55 GWAS consortia with at least 1 US member that met the GWAS consortium definition developed for this analysis. Among these 55 consortia, 30 (55%) had a dedicated website for the consortium, and only 14 (25%) had publicly accessible guidelines from that website. Thus, only one-fourth of the identified GWAS consortia had publicly accessible policies and procedures relevant to the operation of those consortia. Furthermore, although the guidelines that are available generally provide information on the organization and governance of each consortium and on research procedures and protocols, only half of the guidelines address IRB approval procedures, and the level of detail on publication, authorship, data-sharing, and intellectual property policies varies considerably. Although a full comparison of 41 consortia without US members identified in the NHGRI catalog was beyond the scope of this analysis, only 4 (9.8%) have publicly accessible guidelines on their websites, demonstrating a similar trend among international consortia.
Many GWAS consortia are formed for the purpose of enlarging a study’s sample size to increase statistical power, while others are broader collaborations with a GWAS component. Thus, by definition, such consortia consist of large numbers of investigators, research centers, or studies that must collaborate effectively to successfully complete and publish results from a GWAS analysis. Most consortia with guidelines identified in this analysis were formed to study 1 disease or 1 class of diseases, but they differ fundamentally from the traditional model of a single investigator undertaking a defined research study. As a result, guidelines to effectively and fairly govern these efforts are essential, including guidelines for phenotype harmonization (29
). However, most recommendations for the responsible conduct of collaborative research were developed before these large-scale consortia became commonplace (31
). Our analysis demonstrates that only a fraction of GWAS consortia have publicly available guidelines, although some well-developed examples exist (16
). Without additional information from specific consortia, it is impossible to know whether the lack of publicly accessible guidelines reflects a lack of formally adopted guidelines or whether consortia have simply chosen to keep their guidelines accessible to members only. To the extent that consortia are choosing to keep their guiding principles out of public view, this represents a lost opportunity, both with regard to educating others about the successful pursuit of collaborative research and with regard to demonstrating responsible practice to a wider range of interested stakeholders (research participants, funders, etc.).
Recently, Knoppers et al. (34
), from the Public Population Project in Genomics, the European Network for Genetics and Genomic Epidemiology, and the Centre for Health, Law, and Emerging Technologies, proposed a “Code of Conduct” for international genomic research, consisting of 7 principles and procedures: quality, accessibility, responsibility, security, transparency, accountability, and integrity. This guidance is based on the values of “ (i) mutual respect and trust between scientists, stakeholders and participants; and (ii) a commitment to safeguarding public trust, participation and investment” (34, p. 46). Based on the analysis presented here, the limited number of guidelines that are currently publicly available reduces the ability to determine whether GWAS consortia procedures are consistent with these proposed principles. Further, greater transparency of guidelines would allow new consortia to build on the prior experience of existing consortia. For example, recommendations about effective organization structures, recommendations about the level of detail needed for research protocols, and guidelines for when IRB approvals are needed for consortium projects would facilitate establishment of new collaborative arrangements.
There were several limitations of this analysis. First, the NHGRI catalog captures only a subset of all active consortia undertaking large-scale genomic research. For example, the Epidemiology and Genomics Research Program of the National Cancer Institute supports 44 consortia that are investigating a variety of types of cancer (35
). Thirty-five of these consortia meet the GWAS consortium definition used in this analysis. Of these, 8 consortia had published results from a GWAS as of April 1, 2011, and thus were included in the NHGRI catalog and in our analysis. Among the remaining 27 consortia, 17 (63%) were found to have websites, a somewhat larger proportion than the consortia identified from the NHGRI database with websites (30 of 55; 55%). Still other consortia did not yet have GWAS publications in the NHGRI catalog as of April 1, 2011—for example, the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Study, which published the design of the study in 2010 (36
Second, there were limitations to our method for identifying consortia publications because of long consortium names, because of consortium abbreviations with other meanings, and because the names of consortia do not appear in consistent form in author lists or abstracts. In addition, although some consortia were formed specifically for the purpose of performing a GWAS, others are part of broader research collaborations. The latter type of consortia may have guidelines embedded within a more general framework of consortium policies, rather than having specific policies for the GWAS component, and thus may not have been included in this analysis.
Despite these limitations, the ascertainment scheme used here was sufficient to begin broadly describing collaborative practices in this quickly evolving scientific area. Next steps in this research will include a survey of existing GWAS consortia members to provide a more thorough evaluation of the available guidelines and to begin an iterative process for the development of models and recommendations to facilitate large-scale collaborative research. Such a process will need to involve all relevant stakeholders, including investigators, IRB members, and study participants. For example, in GWAS studies funded by the National Institutes of Health, IRB approvals and data-sharing plans are already required, providing one mechanism with which to begin standardizing policies.
As innovative genomic technologies develop, especially DNA sequencing, it is clear that large-scale research collaborations will continue. Some of these consortia will build on those that were developed for GWAS, and others will be formed to address new scientific goals. For example, participants in a Human Genome Epidemiology Network workshop presented a vision for GWAS collaboration “to create a sustainable, credible knowledge base on genetic variation and human diseases… [that] involves [the collaboration of] research investigators, systematic reviewers, online publishers, and database developers” (37
, p. 275). Thus, the need for well-founded guidelines to address collaborative practices and define norms for responsible conduct in this leading-edge research domain will only increase. Wider availability of consortia guidelines would allow for review of the current policies on data-sharing, authorship, publication, intellectual property, and return of results to participants and the development of consensus on appropriate standards that could be uniformly implemented among large-scale consortia. This would not only assist in developing a consistent set of “best practices” to guide genomic research practice but also provide a sound basis from which interested stakeholders (e.g., funders, investigators, research participants) might judge the relative effectiveness of specific collaborative undertakings.
In summary, 55 distinct GWAS consortia were identified from 845 GWAS publications for this analysis, yet only 14 of these have publicly accessible research guidelines on consortia websites. Most of the available guidelines include information on the organization and governance of the consortium, as well as research protocols, but only half address IRB approval procedures. Importantly, the documentation of policies on publication, authorship, data-sharing, and intellectual property varies considerably. Wider availability of consortia guidelines is needed to identify and implement appropriate research standards with broad applicability to emerging forms of large-scale collaboration.