Defining familial longevity and developing a familial longevity score for unbiased epigenetic studies in a birth cohort

<b>Aim:</b> Longevity accumulating in families has genetic and epigenetic components. To study early and unbiased epigenetic predictors of longevity prospectively, a birth cohort would be ideal. However, the original family longevity selection score (FLoSS) focuses on populations of elderly only. <b>Methods:</b> In the German birth cohort KUNO-Kids we assessed when information for such scores may be best collected and how to calculate an adapted FLoSS. <b>Results:</b> A total of 551 families contributed to adapted FLoSS, with a mean score of -0.15 (SD 2.33). Adapted FLoSS ≥7 as a marker of exceptional longevity occurred in 3.3% of families, comparable to original FLoSS in elderly. <b>Conclusion:</b> An adapted FLoSS from data collectable postnatally may be a feasible tool to study unbiased epigenetic predictors for longevity. In the German birth cohort KUNO-Kids we assessed if and how a family longevity selection score may best be calculated to study unbiased epigenetic predictors for longevity in the future. Longevity accumulates in families and genetic as well as epigenetic markers for longevity are overrepresented in some families. To study epigenetic effects causally involved in longevity without a bias, it has to be studied early in life and birth cohorts may be a good chance to do so. However, existing longevity scores have not been developed for that task and it is unclear if they could work in the setting of birth cohort or if the information on previous generations needed to calculate such scores can be collected in birth cohorts. We used the German KUNO Kids Health study, which recruited more than 3000 children since 2015 to test if and when data on longevity can be collected from parents of a newborn and found that parents can give sufficient data on longevity in their families right after birth. We used these data to built an adapted family longevity selection score (FLoSS). We compared the performance of our adapted FLoSS in the KUNO Kids Study to the initial score in classical settings of study populations of old people and found that it lead to very similar distributions of families with aggravated longevity. We compared results of the adapted Floss in detecting families with aggravated longevity to other scores such as Longevity Relatives Count and found that FloSS performs better in birth cohorts. We conclude that using adapted FLoSS to identify families with aggravated longevity at the birth of a child is feasible and a promising opportunity to study early and unbiased epigenetic markers of longevity in the future.