Strengths include the longitudinal design of the study, the high rate of follow-up, the multi-ethnic and population-based sample, the uniquely well characterized cardiovascular risk factors and subclinical cardiovascular disease measures in MESA, use of standardized measures of cognitive function and depression, availability of Apo E genetic data, and ascertainment of both cardiovascular and non-cardiovascular disease endpoints. The gene discussed is APOE; the disease is major depressive disorder.