Table 1.

Disease-related genomics research across three NHGRI research domains. Adapted from Ref. [4].

NHGRI domain	Biology of disease	Science of medicine	Effectiveness of healthcare
Common rubric	Discovery research	Clinical validation	Clinical implementation
General goal	Demonstrate genotype-phenotype associations	Assess outcomes after using genomic information to direct clinical care	Demonstrate improved healthcare with the use of genomic information
Specific examples	Identify persons at increased risk of disease based on their genomic variants Find all variants related to given phenotype or disease Characterize variation in genes known to be related to disease or treatment response Characterize phenotypic variation and effect modifiers in carriers of specific variants Classify patients into subgroups with differing prognosis or treatment response (molecular taxonomy)	Evaluate clinician and patient satisfaction with care after receipt of genomic information Assess impact of reporting incidental findings on health behaviors, healthcare utilization, and psychological well-being Identify causes of rare or undiagnosed diseases Identify sources of infectious disease outbreaks and susceptibilities of infectious agents Compare genome sequencing to enzymatic and other assays for modifiable metabolic disorders in newborns Reclassify intermediate risk patients into high- and low-risk categories where differential interventions are available Validate drug targets and develop improved therapeutic agents	Educate clinicians and patients in clinical use of genomic information Develop clinical informatics systems for reporting results of genomic analyses and providing decision support Evaluate impact of using genomic variant information to individualize treatment Incorporate genomic information into electronic medical records that can follow patients across care systems and throughout lifespan Define clinically actionable genomic variants and disseminate that information and its relevant evidence base