Risk Assessment and Communication Tools for Genotype Associations with Multifactorial Phenotypes: The Concept of "Edge Effect" and Cultivating an Ethical Bridge between Omics Innovations and Society

Ozdemir V., Suarez-Kurtz G., Stenne R., Somogyi A. A. , Someya T., Kayaalp S. O. , ...More

OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY, vol.13, no.1, pp.43-61, 2009 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 13 Issue: 1
  • Publication Date: 2009
  • Doi Number: 10.1089/omi.2009.0011
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.43-61
  • Hacettepe University Affiliated: Yes


Applications of omics technologies in the postgenomics era swiftly expanded from rare monogenic disorders to multifactorial common complex diseases, pharmacogenomics, and personalized medicine. Already, there are signposts indicative of further omics technology investment in nutritional sciences (nutrigenomics), environmental health/ecology (ecogenomics), and agriculture (agrigenomics). Genotype-phenotype association studies are a centerpiece of translational research in omics science. Yet scientific and ethical standards and ways to assess and communicate risk information obtained from association studies have been neglected to date. This is a significant gap because association studies decisively influence which genetic loci become genetic tests in the clinic or products in the genetic test marketplace. A growing challenge concerns the interpretation of large overlap typically observed in distribution of quantitative traits in a genetic association study with a polygenic/multifactorial phenotype. To remedy the shortage of risk assessment and communication tools for association studies, this paper presents the concept of edge effect. That is, the shift in population edges of a multifactorial quantitative phenotype is a more sensitive measure (than population averages) to gauge the population level impact and by extension, policy significance of an omics marker. Empirical application of the edge effect concept is illustrated using an original analysis of warfarin pharmacogenomics and the VKORC1 genetic variation in a Brazilian population sample. These edge effect analyses are examined in relation to regulatory guidance development for association studies. We explain that omics science transcends the conventional laboratory bench space and includes a highly heterogeneous cast of stakeholders in society who have a plurality of interests that are often in conflict. Hence, communication of risk information in diagnostic medicine also demands attention to processes involved in production of knowledge and human values embedded in scientific practice, for example, why, how, by whom, and to what ends association studies are conducted, and standards are developed (or not). To ensure sustainability of omics innovations and forecast their trajectory, we need interventions to bridge the gap between omics laboratory and society. Appreciation of scholarship in history of omics science is one remedy to responsibly learn from the past to ensure a sustainable future in omics fields, both emerging (nutrigenomics, ecogenomics), and those that are more established (pharmacogenomics). Another measure to build public trust and sustainability of omics fields could be legislative initiatives to create a multidisciplinary oversight body, at arm's length from conflict of interests, to carry out independent, impartial, and transparent innovation analyses and prospective technology assessment.