Abstract
Recent work shows strong evidence of ancestry-based assortative mating in spouse pairs of the older generation of the Framingham Heart Study. Here, we extend this analysis to two studies of human longevity: the Long Life Family Study (LLFS), and the New England Centenarian Study (NECS). In the LLFS, we identified 890 spouse pairs spanning two generations, while in the NECS we used data from 102 spouse pairs including offspring of centenarians. We used principal components of genome-wide genotype data to demonstrate strong evidence of ancestry-based assortative mating in spouse pairs of the older generation and also confirm the decreasing trend of endogamy in more recent generations. These findings in studies of human longevity suggest that spouses marrying into longevous families may not be powerful controls for genetic association studies, and that there may be important ethnicity-specific, genetic influences and/or gene–environment interactions that influence extreme survival in old generations. In addition, the decreasing trend of genetic similarity of more recent generations might have ramifications for the incidence of homozygous rare variants necessary for survival to the most extreme ages.
Highlights
One of the surprising findings that has emerged from the Long Life Family Study (LLFS) – a longitudinal family-based study of longevity and healthy aging – is that spouses of members of longevous families tend to be healthier than average
The withinspouse correlation of PC2 (r = 0.20, 95%CI = 0.01; 0.38, p-value = 0.04142) is lower compared to LLFS offspring but remains significantly different from 0 and is consistent with the observation in the LLFS offspring generation, again suggesting decreased ethnicity homogeneity among married couples among offspring
Our analysis showed significant positive correlation between PC1 of spouse pairs that ranged from 0.79 for LLFS proband generation, to 0.67 for New England Centenarian Study (NECS) offspring generation, and to 0.63 for LLFS offspring generation
Summary
One of the surprising findings that has emerged from the Long Life Family Study (LLFS) – a longitudinal family-based study of longevity and healthy aging – is that spouses of members of longevous families tend to be healthier than average. In Sebastiani et al (2013), we showed that spouses of LLFS probands and their siblings have delayed onset of morbidity compared to controls enrolled in the New England Centenarian Study (NECS). A recent article by Pedersen et al (2017) showed that the mortality of spouses marrying into the longevity-enriched families of LLFS was substantially lower than the mortality in a background population matched by birth year and sex. One obvious explanation for the spouses being so healthy is that they share the same environment as the participants from longevous families. Another contributing explanation, we hypothesize, is assortative mating – a pattern of sexual selection in which individuals with similar phenotype(s) and similar genotypes mate more frequently than randomly. We are not aware of genetic studies supporting this latter hypothesis
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