Only 2 such variants have previously been associated with an increased risk of AD in the AD&FTD Mutation Database and Parkinson Disease Mutation Database25: (1) TREM2, p.Arg47His, detected in 2 participants with later-than-expected intergenerational difference in AAO and 1 participant with earlier-than-expected intergenerational difference in AAO; and (2) PLD3, p.Val232Met, detected in 1 participant with later-than-expected intergenerational difference in AAO. The gene discussed is TREM2; the disease is Alzheimer disease.