Ethical Approaches to Genotype-Driven Research Recruitment

Many genotype and genome-wide association studies (GWAS) are conducted using a phenotype-driven approach: cases and controls are identified based on the presence or absence of a particular condition and analyses are undertaken to identify gene variants associated with that condition. The inverse--a genotype-driven approach--is receiving increasing attention as another powerful tool for understanding the impact of genetic variation. Cases and controls are defined among existing study populations based on the presence or absence of a particular genotype, and in-depth phenotyping is then conducted to understand the relationship between observable traits and the gene variant of interest. Enabling such a bottom-up approach to identifying and recruiting participants for follow-up studies could significantly advance the pace of genomic research by expanding the existing mechanisms for studying the functional significance of human genetic variation. Such approaches, however, present ethical challenges that have not been fully addressed. Genotype-driven recruitment is inextricably linked to the complex and much-debated issue of disclosing individual research results: when individuals are recontacted, what if anything should they be told about the genotype that led to their being recontacted? There is a fundamental tension between avoiding the introduction of potentially unwanted and uncertain information, and avoiding deception when explaining to prospective participants the purposes of the research and why they are being approached for participation. The purpose of this project is to develop evidence-based guidelines for addressing the ethical issues that arise in genotype-driven recontact and research recruitment. Specifically, this project involves 3 Clinical and Translational Science Award (CTSA) sites that will collaborate to:

Explore the perceptions of research participants who have experienced genotype-driven recontact for further research participation.
Investigate IRB chairs experiences, opinions, and concerns about genotype-driven recontact and research recruitment.
Formulate guidelines to assist IRBs and researchers in identifying balanced approaches to genotype-driven recontact and research recruitment.