Longevity Relatives Count score identifies heritable longevity carriers and suggests case improvement in genetic studies

Abstract

<jats:title><jats:bold>Abstract</jats:bold></jats:title><jats:p>Longevity loci represent key mechanisms of a life-long decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long-lived cases with the heritable longevity trait amongst long-living phenocopies. To avoid phenocopies, family selection scores have been constructed but these have not yet been adopted as state of the art in longevity research. Here we aim to identify individuals with the heritable longevity trait by using current insights and a novel family score based on these insights. We use a unique dataset connecting living study participants to their deceased ancestors covering 37,825 persons from 1,326 five-generational families, living between 1788 and 2019. Our main finding suggests that longevity is transmitted for at least 2 subsequent generations only when at least 20% of all relatives are long-lived. This proves the importance of family data to avoid phenocopies in genetic studies.</jats:p>

Mothers of small-bodied children and fathers of vigorous sons live longer

“…Age at death in humans is heritable [maximum h 2 = 0.25–0.4; reviewed by ( 15 – 17 )] with genetic influence increasing with age ( 18 , 19 ). Also, longevity (defined here as belonging to the 90th percentile of the lifespan of the population) correlates genetically with multiple diseases and traits, such as coronary artery disease ( r g = −0.40), age of first birth ( r g = 0.33) and years of schooling ( r g = 0.26) ( 20 ).…”