Skip directly to local search Skip directly to A to Z list Skip directly to navigation Skip directly to site content Skip directly to page options
CDC Home


HuGENet™ Workshops

Assessment of Cumulative Evidence on Genetic Associations: International Workshop held in Venice (Italy) on 9-10 November 2006

Many gene variants have been assessed in relation to a wide range of outcomes, and an increasing number of genetic factors are being investigated in relation to any one specific outcome.  For decision making, it would be valuable to integrate evidence for different genetic factors for one outcome, and for multiple outcomes in relation to a specific genetic factor. The publication of synopses of the cumulative evidence on genetics and population health in specific fields could address a gap resulting from the fact that systematic reviews and meta-analyses tend to focus only on one or a few specific gene-disease associations at a time. However, a prerequisite is to agree on widely acceptable criteria for assessing cumulative evidence.

Several assessment schemes have been proposed (1-8), but some overlap with the assessment of single studies, and the schemes differ from one another. Considerations for inferring causation from observational studies of associations between exposures and disease were proposed in the 1960s (9, 10) and have been modified for different field of epidemiological investigation (11-13). However, the relevance of these considerations to current and evolving challenges of human genome epidemiology needs to be assessed.

Following the initial meeting of the Network of Networks in October 2005 (14), a HuGENet Working Group on the Assessment of Evidence was established. This Group reviewed evidence on assessment and grading schemes from other biomedical fields, and discussed options for developing schemes specific to genetic associations. A workshop was organized in Venice on November 9-10, 2006 where a multi-disciplinary panel of around 25 experts discussed these issues. The panel discussed existing assessment schemes from other fields, experiences of developing synopses of cumulative evidence on diverse diseases, attempts to link human genome epidemiology with other biological and experimental evidence relevant to acute, infectious, and chronic diseases, the framework for causal inference, and methods for the efficient assessment of quantity and quality of cumulative evidence.

An initial set of guidelines was agreed and will be refined over the coming months. The workshop presentations will shortly be made available on the Canadian HuGENet Coordinating Centre Web site ( The development of a system of assessment of cumulative evidence on genetic associations and related interactions is likely to be iterative, and will be informed by further experience gained in developing synopses of cumulative evidence (15). In addition, further work is ongoing about linking these guidelines with biological and experimental evidence.

Section Content


Setting the stage: what we know and what others have done


Experiences of developing synopses of cumulative evidence on  diverse diseases


Linking human genome epidemiology with other biological and  experimental evidence


Framework for causal inference


Assessment of quantity and quality of cumulative evidence


  1. Weiss ST. Association studies in asthma genetics. American Journal of Respiratory and Critical Care Medicine 2001; 164:2014-2015.
  2. Cooper DN, Nussbaum RL, Krawczak M. Proposed guidelines for papers describing DNA polymorphism-disease associations. Hum Genet 2002; 110:208.
  3. Huizinga TW, Pisetsky DS, Kimberly RP. Associations, populations, and the truth: recommendations for genetic association studies in Arthritis & Rheumatism. Arthritis & Rheumatism 2004; 50:2066-2071.
  4. Rebbeck TR, Martinez ME, Sellers TA, Shields PG, Wild CP, Potter JD. Genetic variation and cancer: improving the environment for publication of association studies. Cancer Epidemiology, Biomarkers & Prevention 2004; 13:1985-1986.
  5. Freimer NB, Sabatti C. Guidelines for association studies in Human Molecular Genetics. Hum.Mol.Genet. 2005; 14:2481-2483.
  6. Wacholder S. Publication environment and broad investigation of the genome. Cancer Epidemiol.Biomarkers Prev. 2005; 14:1361.
  7. Anonymous Framework for a fully powered risk engine. Nat.Genet. 2005; 37:1153.
  8. Ioannidis JP. Commentary: Grading the credibility of molecular evidence for complex diseases. Int.J.Epidemiol. 2006; 35:572-578.
  9. Surgeon General (Advisory Committee). Smoking and health. US Department of Health, Education and Welfare, Washington, DC, 1964.
  10. Hill AB. The environment and disease: association or causation? Proc.R.Soc.Med. 1965; 58:295-300.
  11. Weed DL, Gorelic LS. The practice of causal inference in cancer epidemiology. Cancer Epidemiol Biomarkers Prev 1996; 5:303-311.
  12. Potischman N, Weed DL. Causal criteria in nutritional epidemiology. Am.J.Clin.Nutr. 1999; 69:1309S-1314S.
  13. International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans; preamble. 2006;1-27.[PDF 222 KB]
  14. Ioannidis JP, Bernstein J, Boffetta P, Danesh J, Dolan S, Hartge P, Hunter D, Inskip P, Jarvelin MR, Little J, Maraganore DM, Bishop JA, O'Brien TR, Petersen G, Riboli E, Seminara D, Taioli E, Uitterlinden AG, Vineis P, Winn DM, Salanti G, Higgins JP, Khoury MJ. A network of investigator networks in human genome epidemiology. Am.J.Epidemiol. 2005; 162:302-304.
  15. Ioannidis JP, Gwinn M, Little J, Higgins JP, Bernstein JL, Boffetta P, Bondy M, Bray MS, Brenchley PE, Buffler PA, Casas JP, Chokkalingam A, Danesh J, Smith GD, Dolan S, Duncan R, Gruis NA, Hartge P, Hashibe M, Hunter DJ, Jarvelin MR, Malmer B, Maraganore DM, Newton-Bishop JA, O'Brien TR, Petersen G, Riboli E, Salanti G, Seminara D, Smeeth L, Taioli E, Timpson N, Uitterlinden AG, Vineis P, Wareham N, Winn DM, Zimmern R, Khoury MJ, Human Genome Epidemiology Network and the Network of Investigator Networks. A road map for efficient and reliable human genome epidemiology. Nat.Genet. 2006; 38:3-5.



Contact Us:
  • Centers for Disease Control and Prevention
    1600 Clifton Rd.
    Atlanta, GA 30333 USA
    800-CDC-INFO (800-232-4636)
  • Additional information for Public Health Genomics is available on our contact page. The U.S. Government's Official Web PortalDepartment of Health and Human Services
Centers for Disease Control and Prevention   1600 Clifton Road Atlanta, GA 30329-4027, USA
800-CDC-INFO (800-232-4636) TTY: (888) 232-6348 - Contact CDC–INFO
A-Z Index
  1. A
  2. B
  3. C
  4. D
  5. E
  6. F
  7. G
  8. H
  9. I
  10. J
  11. K
  12. L
  13. M
  14. N
  15. O
  16. P
  17. Q
  18. R
  19. S
  20. T
  21. U
  22. V
  23. W
  24. X
  25. Y
  26. Z
  27. #