The nearest neighboring genes to these markers in the FRA6E region were PLG and MAP3K4. PLG is a circulating zymogen with the primary function of dissolving fibrin (OMIM #173350). PLG is not an established candidate gene for SA but has been suggested to be involved with wasting (weight loss and poor wound healing) and decreased longevity due to disseminated fibrin deposition in animal model studies (Cheng et al. 2005). There is no established biological evidence implicating MAP3K4 with longevity or aging.

A potential limitation to our study was the inability of MQLS to allow for covariate adjustment, and as a result we were unable to adjust for heterogeneity in study findings across ascertainment centers (Ohio and Indiana). However, our linkage analyses should implicitly take care of confounding through pedigree structure. Since we looked at a consensus of results across linkage and association analyses, we believe that the results are not likely confounded by ascertainment center and merit further follow-up.