Reporting genetic association studies: the STREGA statement

Abstract

[...] for the suggested relation between several genetic polymorphisms and occurrence of sepsis in human beings, systematic review in 2006 of the study reports showed that the information needed to assess the risk of bias was lacking.3 Results of medical research need to be reported with sufficient accuracy and transparency to enable critical appraisal.

The completion of sequencing of the human genome created high hopes for the translational potential of knowledge from genetic association studies. The combination of advances in genomic and related technologies and methods of conventional epidemiology has produced one of the most dynamic fields of medical research. Genome-wide association studies have led to an unparalleled growth and improved accuracy in genetic information.1 At the same time, the complexity of the available data has increased substantially. However, advances in the application of this knowledge, such as determination of an individual's risk of disease or development of personalised therapies, might not become available as quickly as expected.2 The devil is in the detail. For instance, for the suggested relation between several genetic polymorphisms and occurrence of sepsis in human beings, systematic review in 2006 of the study reports showed that the information needed to assess the risk of bias was lacking.3

Results of medical research need to be reported with sufficient accuracy and transparency to enable critical appraisal. Reporting guidelines aim to improve the research literature by the use of checklists with items deemed essential by multidisciplinary working groups.4 The STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) statement was developed to help authors to improve the reporting of cross-sectional, case-control, and cohort studies.5 Genetic association studies that use one of these study designs present several specific challenges. As part of its road map for human-genome epidemiology, the Human Genome Epidemiology Network set up a working group to provide guidance on how to report these studies.6 This initiative, called STrengthening the REporting of Genetic Association studies (STREGA), elaborated on the STROBE statement. The resulting STREGA statement was recently published in several journals simultaneously.7 The STREGA checklist provides additions to 12 of the 22 items of the STROBE checklist to cover crucial aspects of genetic epidemiology reporting (table). Each of these areas has a rationale given.7

In the fast-moving field of genetic association studies, the risk of new methodological pitfalls is high. The effects of individual variants in common disorders are almost always modest. Generally, the credibility of gene-disease associations is low if the evidence comes from single studies of small scale and cannot be replicated. Genetic evidence can only transform the prevention, diagnosis, or therapy of diseases if it is consistent and strong. The STREGA statement is neither prescriptive, nor does it pass judgment on how researchers have done their studies. Rather, the statement advocates for transparency in reporting how a study was done. This transparency might help to inform the design, conduct, and analysis of future studies, and improve the reliable integration of evidence from multiple studies. STREGA can help authors to include the essential information in reports of both smaller association studies and large-scale analyses of data from several sources. Earlier reporting guidelines, such as the CONSORT statement, have also proven useful for peer reviewers and editors.8 Evidence emerges that they also helped to improve the quality of research reports.9 The endorsement by journals-eg, in instructions for authors or reviewers-will be key to the success of the STREGA statement and of other reporting guidelines. If, on top of enhanced accuracy and transparency, the STREGA recommendations can help to make articles on genetic association studies an easier read for both specialised and less proficient readers, it will have served its purpose.

References

1 McCarthy MI, Abecasis GR, Cardon LR, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008; 9: 356-69.

2 Ioannidis JP. Personalized genetic prediction: too limited, too expensive, or too soon? Ann Intern Med 2009; 150: 139-41.

3 Clark MF, Baudouin SV. A systematic review of the quality of genetic association studies in human sepsis. Intensive Care Med 2006; 32: 1706-12.

4 Altman DG, Simera I, Hoey J, Moher D, Schulz K. EQUATOR: reporting guidelines for health research. Lancet 2008; 371: 1149-50.

5 von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370: 1453-57.

6 Ioannidis JP, Gwinn M, Little J, et al. A road map for efficient and reliable human genome epidemiology. Nat Genet 2006; 38: 3-5.

7 Little J, Higgins JP, Ioannidis JP, et al. STrengthening the REporting of Genetic Association studies (STREGA): an extension of the STROBE statement. Hum Genet 2009; 125: 131-51. http://www.medicine.uottawa. ca/public-health-genomics/web/assets/documents/Final- STREGA%20manuscript-Feb2%202009.pdf (accessed June 22, 2009).

8 Moher D, Simera I, Schulz KF, Hoey J, Altman DG. Helping editors, peer reviewers and authors improve the clarity, completeness and transparency of reporting health research. BMC Med 2008; 6: 13.

9 Plint AC, Moher D, Morrison A, et al. Does the CONSORT checklist improve the quality of reports of randomised controlled trials? A systematic review. Med J Aust 2006; 185: 263-67.