Discrimination of the classification rule based on the ensemble of 281 genetic risk models.

Abstract

<p><b>Panel A:</b> Posterior probability of exceptional longevity (EL) and average longevity (AL) (x axis) in the centenarians (red boxplots) and controls (AL1: Illumina controls, blue boxplots, AL2: NECS controls, green boxplots) of the discovery set (NECS, top left). Both sensitivity and specificity were 89%. The boxplots in blue and green show that the distributions of the posterior probability of EL in the two control groups are not statistically different (p-value from t-test comparing the posterior probability of EL = 0.21). <b>Panel B:</b> Posterior probability of EL and AL (x axis) in the centenarians (red boxplots) and controls of the replication set 1. Sensitivity and specificity were 60% and 58% and the distributions of the predictive score are significantly different (t-test p-value = 0.001). <b>Panel C:</b> Median values of the posterior probability of EL (predictive score) in subsets of centenarians of the replication set 1 with increasing ages. The barplot shows that the median score increases with older ages. <b>Panel D: Sensitivity of the classification rule in subsets of centenarians of the replication set 1 with increasing ages.</b> The barplot shows the increasing sensitivity in older groups that reaches 85% in 20 subjects aged 106 and older. <b>Panel E: Distribution of the posterior probability of exceptional longevity in the 253 cases of the replication set divided into two age groups (<103 years, pale blue, mean age 99 years, and ≥103 years, red, mean age 106).</b> The sensitivities in the two groups are 57% and 71.4%. The three distributions are significantly different (p-value = 0.04 from t-test comparing Illumina controls and centenarians aged <103; p-value = 0.004 from t-test comparing the centenarians stratified by age). <b>Panel F: Sensitivity and specificity in an additional set of 2863 controls from the Illumina database (blue), and an additional set of 60 centenarians that include 39 centenarians enrolled since June 2009 (mean age 108) and 21 centenarians that were excluded from older analysis because of genetic matching (mean age 106).</b> The specificity in the additional Illumina controls is 61.2%. The sensitivity in the additional centenarians was 71.5% in the set of 21, and 82% in the additional 39 for a total of 78% (p-value from t-test comparing the posterior probabilities of EL in controls and centenarians <1e-10).</p