TABLE 1.

Implications of research topic and message to participants: Hypothetical examples

Study	Main findings	Implications for participants	Main message in return of aggregate results
Genome-wide association study (GWAS) to identify gene variants associated with height	Multiple common gene variants identified, each with small effect; findings together explain only a small portion of heritability of height	No medical significance; results unlikely to generate anxiety	Provide clear explanation of small effect of identified variants, and likelihood that other genetic factors will be found. Explain how this knowledge contributes to better scientific understanding of genetic contribution to physical traits.
GWAS to identify gene variants associated with type 2 diabetes (T2DM)	Multiple common gene variants identified, each with small effect; findings together explain 20% of heritability of T2DM	Participants (particularly those not currently affected by T2DM but who may be at increased risk of future disease) may be interested in personal results	Provide clear explanation of small effect of variants; in addition, explain preventive measures for T2DM, and that current medical recommendations would not change based on results. Explain next steps, e.g., to determine whether genetic information would have clinical utility if added to established risk assessment techniques such as family history.
Candidate variant study to determine predictive value of gene variant associated with adverse drug effect. All participants have been on drug in question sufficiently long to know whether or not they will have adverse reaction	Study suggests moderate positive predictive value and high negative predictive value of genotype for adverse drug reaction	Participants may wish to know their genetic status for use in clinical care; however, clinical utility of the information for study participants is low because they have already been treated and their reaction status is known	As relevant, explain need to replicate and need to develop test protocol for clinical lab, prior to clinical use. Also explain limited relevance to study participants. This study represents an example where researcher may consider returning individual results, depending on status of test validation and potential to inform future drug prescribing
Family-based study using whole exome sequencing, to identify gene associated with rare, untreatable X-linked recessive genetic disease	Gene and causative mutations identified	Some family members, in particular sisters of affected, may benefit from testing based on study results, to determine whether they are carriers for the disorder	Explain results, emphasizing that they do not have any immediate treatment implications, but will assist researchers to understand the disease better, with potential clinical benefits in the future (likely a long time lag).This is an example where researchers are likely also to feel an obligation to return individual results.