A genome-wide association study identified 10 novel genomic loci associated with intrinsic capacity

Abstract

In 2015, the World Health Organization introduced the concept of intrinsic capacity (IC), a composite of all the physical and mental attributes that contribute to healthy aging. While substantial evidence supports the biological basis of IC and its subdomains, the extent of genetic influence on IC remains largely unexplored, with no studies currently available. Understanding the genetic basis of IC is crucial to advancing our knowledge and identifying interventions that promote healthy aging. To investigate the genetic basis of IC, we used data from the UK Biobank (UKB; N=44,631) and the Canadian longitudinal study on aging (CLSA; N=13,085). We estimated SNP-based heritability (h2SNP) at 25.2% in UKB and 19.5% in CLSA. A Genome-Wide Association Study (GWAS) identified 38 independent SNPs for IC across 10 genomic loci and 4,289 candidate SNPs, mapped to 197 genes. Post-GWAS analysis revealed the role of these genes on cellular processes such as cell proliferation, immune function, metabolism, and neurodegeneration, with high expressions in muscle, heart, brain, adipose, and tibial nerve tissues. Of the 52 traits tested, 23 showed significant genetic correlations with IC, and a higher genetic loading for IC was associated with higher IC scores. This study is the first to identify genetic variants and pathways associated with IC, providing a foundation for future research on healthy aging.