Obesity Related to Antipsychotic Liability & Exposure (ORAcLE) Genetics Consortium

ORAcLE is the first genetics consortium completely devoted to investigating genes related to antipsychotic-induced weight gain and metabolic dysfunction. We are the first to combine clinical trials with data from existing health systems. We are also working to extend public-private partnerships to better understand the problem of antipsychotic-induced weight gain.

As the project gets underway, we will send a document with proposed analyses.  These include a list of initial analyses — those that would be used to generate a first-pass meta-analysis to get an initial sense of the results — and sometimes a list of likely follow-up analyses, including those that would be important for publication of a paper. Our initial analyses are likely to focus on longitudinal changes in body weight and body mass index (BMI) after exposure to antipsychotics. In addition to typical stratified analyses by ancestry groups, we may examine stratification by sex and/or class of medication. Another key component of our analysis goals is to determine the extent of differences across the age spectrum, so we may also consider analyses stratified by age groups.

Investigators who are actively participating in an ORAcLE project, such that they would be named authors in a paper, are considered ORAcLE investigators.  In addition, if someone is a longstanding close collaborator within a cohort/study contributing GWAS or similar data to ORAcLE, but that person happens not to be a named author on an ORAcLE paper, that person is also an ORAcLE investigator despite not being named as an author on any particular paper.

ORAcLE investigators are periodically privy to confidential results — such as the loci that are near the top of a meta-analysis list — and are expected to keep these results confidential.

An investigator who is not participating in ORAcLE but happens to be in the same institution as an ORAcLE investigator or who happens to participate in a non-ORAcLE consortium with an ORAcLE investigator is not an ORAcLE investigator (and is not allowed access to confidential ORAcLE results).

ORAcLE investigators can also participate in working groups, if they have the time and the interest to contribute to the work involved in acquiring datasets, QCing data for analysis, meta-analysis, and/or carrying out follow-up analyses.  Typically, these consist a central analysis group (for QC and basic analyses), and potentially additional groups for specific trait analyses, or groups for separate secondary analysis purposes that may arise over time.

The Steering Committee for the ORAcLE project involves senior, key investigators, consultants, and collaborators who contributed significantly to the design of the overall study and are responsible for overseeing the conduct of the proposed work. Steering Committee members perform key roles in the administrative aspects of day-to-day study operations and ensure the highest ethical principles and scientific rigor in the conduct of the proposed work.

Cohorts and investigators that are participating in ORAcLE (whether they have contributed GWAS data or are replication cohorts) will be recognized with authorship on ORAcLE manuscripts. Authorship guidelines for papers are listed below.

The cohorts (and possibly other consortia) participating in ORAcLE are all recognized individually in multiple ways. These are the same for cohorts that contribute GWAS data or replication data:

1. Inclusion of authors from these cohorts/consortia
2. Explicitly by naming the cohorts (and consortia, if desired) in the author contribution section
3. Describing and naming the cohorts/consortia in the Acknowledgements, Methods, Supplementary Information, or Supplementary Tables sections of submitted manuscripts

For cohorts that contribute GWAS data, ORAcLE rules apply: no surprises, coordination of publications, participation in coordinated analyses, etc. Simultaneously contributing the same unpublished data to multiple meta-analysis papers performing the same analyses is prohibited, as this could result in overlap, internal competition, and double publication.

Due to potential for this project to include scientific contributions from both industry and academia, we’re keenly aware of potential financial and clinical implications of any real or perceived conflict of interest. We ask that consortium members disclose any relationships or interests that may pose a potential conflict of interest. All ORAcLE investigators are asked to disclose known or anticipated conflicts of interest to the Steering Committee as soon as possible, so that we may coordinate publication priorities and avoid cross-consortia conflicts with potentially overlapping meta-analyses.

Replication cohorts will remain under less stringent rules — particularly since they may well be participating in their own consortia that are planning on publishing separate GWAS data. These groups correspondingly have access to less information — essentially just the list of variants being replicated — but also are free to publish their own GWA studies. However, disclosure of potential conflicts is encouraged.

For work beyond primary papers, we will maintain a list of side projects being pursued by ORAcLE investigators related to the goals of the consortium and expect ORAcLE investigators to openly disclose these related projects. Such projects generally fall into two categories: 

1. Those that use the results (including pre-publication results) of meta-analyses that have already been generated by ORAcLE
2. Those that require additional analyses of ORAcLE data.

Examples of the former might be to test whether the proven variants from the ORAcLE meta-analysis have associations with other traits not covered by ORAcLE (such as general obesity, other antipsychotic side effects, efficiency measures, etc.), or to take the proven ORAcLE loci forward for functional analyses or further genetic characterization such as deep resequencing. An example of the latter might be to look for gene-gene interactions within the ORAcLE datasets (which would require coordinated additional analyses across ORAcLE investigators). We emphasize that this disclosure is both necessary for the fairness and openness of the consortium, but also for the collaborative nature and success of these side projects.

If an investigator wishes to use a set of GWAS data for additional analysis, then participation in such projects is open to all groups who have contributed those GWAS data. If multiple groups are pursuing the same ideas, they agree to coordinate as much as possible, either by combining the work into one paper, or coordinating publication, unless severe differences in timing (more than 1-3 months) would cause undue delay for one of the groups. If there is potential overlap, the groups must communicate to determine the extent of overlap and come to a resolution for how to proceed.

Non-ORAcLE investigators can also request data beyond what is made publicly available (see below). These are submitted as formal look-up requests. Where there is conflict with internal ORAcLE side projects, typically the internal project would take precedence, and the lookup would proceed only after discussion with the internal side project investigators.

While authorship is decided on an individual basis for each paper (depending on contribution), the model listed below, derived from the most up to date International Committee of Medical Journal Editors Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals. Variations on these guidelines have been used across several consortia, and reflects principles we consider important to the integrity of the scientific process. This model has seven groups of authors:

1. Early career investigators (e.g. post-doctoral research scholars, investigators at the instructor or assistant professor level) who strongly led the efforts, including writing, and analysis, study design, or interpretation of findings, costarred as first authors.
2. Early career investigators who also had substantial contributions to the paper, such as active members of the working group, major participants in data cleaning/meta-analysis, and those who performed key specialized analyses such as those that ended up as a figure/table in the paper.
3. In alphabetical order, early career investigators who had substantial individual contributions but not as much as those in Group 1 or 2. Typically, these might be lead analysts or other junior investigators who made a sizable contribution such as GWAS analyses performed specifically for the paper.
4. In alphabetical order, early career and senior (e.g. tenured professors and associate professors) investigators who had contributions worthy of authorship (participating in analysis, phenotype collection, genotyping, oversight of cohorts, etc. that was specific to the paper) but not as much as those in the other groups. Examples include investigators contributing study-specific analyses, replication, or contributing a single analysis conducted on secondary data.
5. In alphabetical order, senior investigators who participated significantly in ORAcLE activities but did not lead/oversee the writing and/or analysis for a manuscript. Typically, these might be members of the steering committee or leaders of other key ORAcLE activities.
6. Senior investigators who had substantial contributions (especially multiple contributions) to writing, analysis, and/or other key activities, or represent consortia with major contributions not otherwise represented by other senior authors.
7. The senior investigators who contributed significantly to the leadership/oversight of analyses and/or manuscript writing, typically with greater contributions than those in group 6, and listed as co-starred senior authors.

Additional considerations for co-starred authors:

A small number of co-starred authors are sometimes included to represent consortia with major contributions, or major contributions to key consortium efforts across a set of papers being published more or less simultaneously. Consideration for authorship in tiers 1 and 2 can be determined by contribution, irrespective of career status. Consideration is also given to balance authorship across groups and institutions when multiple papers are submitted in parallel. 

Total number of authors:

Authorship will be contingent upon fulfilling at least one of the roles listed below in the guidelines. The number of authors for each role should not exceed the limits indicated, which will depend on cohort size and complexity to administer.  If one person fills a role for multiple cohorts, they should be listed each time, and each time counts towards the authorship limits for that cohort. More details on the guidelines are given below. If you feel you need to exceed these limits, please contact Ginger Nicol (nicolg@wustl.edu) and Anne Justice (aejustice1@geisinger.edu).

Authorship guidelines applied in previous studies:

For each cohort, authorship includes investigators who have been instrumental in:

1. Overseeing the entire cohort (1-2 per cohort depending on sample size and/or the complexity of administration of the cohort),
2. Modeling the phenotype data used in this paper (1-2 authors per cohort),
3. Analyzing the genotype-phenotype association data (1-2 authors per cohort), or
4. Generating actual genotype data that were specific for this paper (1-2 per cohort depending on sample size – this would not be relevant for in silico replication).

Additional circumstances impacting author number:

Situations may arise that require lower (i.e. results are submitted from an existing analysis that did not require any new effort) or higher number of study authors (i.e. a large number of analyses are requested from each study, multiple waves of analyses are conducted for testing purposes).  These circumstances will be readdressed by the Steering Committee for each paper as needed.

Participants from a group who have been instrumental in main consortium-wide efforts (such as quality control of summary results, meta-analysis, secondary analyses, etc.) and/or efforts specific to a particular manuscript qualify for authorship independent of their work on cohort-level analysis. These authors would be above and beyond the author list for each cohort, and would be recognized in separate sections of the author list, or in some cases also be co-starred authors.

Secondary or side projects using unpublished data from the ORAcLE consortium should recognize the lead authors of the primary study, list individual data source(s) when appropriate, and reference grant number R01MH122686 in the acknowledgements section of the manuscript. Manuscripts for which ORAcLE consortium members had substantial author-level involvement will listed as co-authors according to the guidelines listed above. Individuals responsible for data contributed to the “ORAcLE” consortium by smaller consortia will be listed in the acknowledgments section of relevant manuscripts, along with the funding source. Individuals who contributed to the ORAcLE study but did not meet criteria for authorship noted above, can be listed in an Appendix in such a way that these authors would NOT be picked up as Collaborators by PubMed.  If journal specifications do not allow this, please notify the ORAcLE Steering Committee so appropriate steps can be taken to avoid undesired mentions of individual authors in PubMed.