Author: Muin J. Khoury
Position: Director, National Office of Public Health Genomics
Institution: Centers for Disease Control and Prevention
E-mail: muk1@cdc.gov
Additional Authors: Julian Litte, Julian Higgins, John P. Ioannidis, Marta Gwinn
Submitted Date: April 14, 2007
Published Date: April 16, 2007
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

We applaud PLoS editors for their commitment to publish high-quality systematic reviews (SRs, 1). Moher et al (2) clearly documented the inconsistent quality of reporting of SRs. With more than 2500 SRs published every year, low quality or outdated reviews may mislead researchers, providers and policy makers. The situation could be improved if more widely agreed-upon, evidence-based reporting guidelines were developed and adhered to.

The growing field of genetic associations (GAs) illustrates the urgent need for transparent systematic reviews and meta-analyses. Already, thousands of articles on GAs have been published and the application of high-throughput genotyping methods may exponentially increase the number of reported associations (3). Selective reporting of large numbers of false-positive associations might undermine the field and interfere with our ability to translate advances in genomics into clinical practice.

To address these problems, the Human Genome Epidemiology Network (HuGENetTM) was started as a global collaboration to strengthen methods of analysis and reporting of GAs and to develop a reliable knowledge base on the association between genetic variation and (4). Between 2001 and 2006, the HuGENetTM online database assembled more than 25,000 published articles on genetic associations and more than 500 systematic reviews of GAs. Nevertheless, there are large inconsistencies in the quality of genetic association studies (5) and in the reporting of SRs of such associations (6). In collaboration with several journals, HuGENetTM promotes the publication of transparently reported SRs of gene-disease associations (4). More than 50 HuGE reviews have been published over the past 6 years.

After several HuGENetTM workshops bringing together researchers from different fields and journal editors, the first edition of a HuGENetTM handbook of systematic reviews¿modeled, in part, after the Cochrane handbook was published on the Canadian HuGENetTM website (7). The handbook describes methodological issues and outlines steps in conducting such reviews, including the need for a detailed protocol. It also discusses meta-analysis methods. We strongly encourage researchers interested in conducting systematic reviews of GAs to consult the HuGENetTM handbook, and adopt transparent protocols. Retrospective SRs of published data have limitations, even when properly conducted. Investigators can advance the field of human genome epidemiology by conducting prospective meta-analyses and large collaborative analyses through international consortia. HuGENet has created a Network of Investigator Networks to help the growth of such initiatives (8).

References

1. PLoS Medicine Editors (2007). Many reviews are systematic but some are more transparent and completely reported than others. PloS Medicine;4(3):e147.
2. Moher D, Tetzlaff J, Tricco AC, Sampson M, Altman DG (2007) Epidemiology and reporting characteristics of systematic reviews. PLoS Med 4(3): e78
3. Khoury MJ, Little, Gwinn M, Ioannidis JP (2006). On the synthesis and interpretation of consistent but weak gene-disease associations in the era of genome-wide association studies. Int J Epidemiol, Dec 20 (Epub)
4. Human Genome Epidemiology Network (HuGENetTM ). Centers forf Disease Control and Prevention. http://www.cdc.gov/genomi...
5. Bogardus ST Jr, Concato J, Feinstein AR (1999). Clinical epidemiological quality in molecular genetic research: the need for methodological standards. JAMA 281:1919-1926.
6. Attia J, Thakkinstian A, D’Este C (2003). Meta analysis of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol 56:297-303.
7. Little J, Higgins J (eds) (2006). HuGENet HuGE review handbook (version 1.0). http://www.genesens.net/_...
8. Ioannidis JPA, Gwinn M, Little J, et al. A road map for efficient and reliable human genome epidemiology. Nat Genet 38:3-5.