Table 3.

Three candidate gene hypotheses presented at the Fifth SIG Meeting.

Researcher-driven hypotheses (with a focus on the genetic variants)	Community-driven hypotheses (with a focus on health condition and outcomes)	Review of information	GRoR	Novelty
Hypothesis #1: Diabetes and kidney disease
Type 2 diabetic patients who carry either the UMOD or TENM3 variants are more likely to have chronic kidney disease.	Known variants that predict: Type 2 diabetic patients who have chronic kidney disease.	UMOD and TENM3 variants have been found to be associated with individuals of European descent.31 UMOD or uromodulin produced only in the kidney plays an important role in kidney and urine function.31 TENM3 or Teneurin Transmembrane Protein 3 has been associated with cholangitis and kidney disorders in the UK Biobank.31	No	High
Hypothesis #2: Hypertension, kidney disease, and racial disparities
Black and Hispanic Americans who carry the MYH9 variants associated with hypertension are at a higher risk of nondiabetic end-stage kidney disease.	Known variants that predict: Black and Hispanic Americans with hypertension who are at a higher risk of end-stage kidney disease.	Partial African ancestry of the MYH9 variants shows increased susceptibility to ESKD.32,33 MYH9 or nonmuscle myosin heavy chain IIA—contributes to cell movement and cell shape. It is thought that a lack of functional myosin IIA leads to the release of large, immature platelets in the bloodstream, resulting in a reduced amount of normal platelets. Platelets prevent clots by plugging up bleeding.33	No	Mid
Hypothesis #3: Pharmacogenetics and racial disparities
Black American patients with diabetes undergoing percutaneous coronary intervention not only have a higher prevalence of high on-treatment platelet reactivity to clopidogrel but also have higher CYP2C19 variant carrier status compared with Non-Hispanic White Americans.	Known variants that predict: Black American patients with diabetes undergoing surgery are more likely to react to Clopidogrel compared with Non-Hispanic White Americans.	Individuals with CYP2C19 variants react to being on the Clopidogrel because it leads to adverse cardiac events. Clopidogrel requires CYP2C19 to become active.34 The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD-GENE) score ≥10 results in an increased risk for blocked arteries events among patients receiving Clopidogrel after surgery.35,36	Yes	Low

GRoR consists of variants assessed and returned to All of Us participants via the participant portal²⁹; The “Review of Information” column provides a summarized literature review, and the “Novelty” column reflects scientific novelty as assessed by the facilitator team, based on available literature and publication volume.

Abbreviation: GRoR, genetic return of results.