A joint analysis of longevity and age-related disease variants for gene expression association

Abstract

A large number of genetic variants associated with human longevity have been reported but how they play their functions remains elusive. We performed an integrative analysis on 113 genome-wide significant longevity and 14,529 age-related disease variants in the context of putative gene expression regulation. We found that most of the longevity allele types were different from the genotype of disease alleles when they were localized at the same chromosomal positions. Longevity variants were about eight times more likely to be associated with gene expression than randomly selected variants. The directions of the gene expression association were more likely to be opposite between longevity and disease variants when the association occurred to the same gene. Many longevity variants likely function through down-regulating inflammatory response and up-regulating healthy lipid metabolisms. In conclusion, this work helps to elucidate the potential mechanisms of longevity variants for follow-up studies to discover methods to extend human healthspan.