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

Beyene, M. B., Visvanathan, R., Alemu, R., Benyamin, B., Bhattacharjee, R., Beyene, H. B., Theou, O., Sumi, Y., Thiyagarajan, J. A., Matteo, C., John, B. R., Amare, A. T.

University of AdelaideUniversity of Adelaide · medrxiv

Paper

Abstract

In 2015, the World Health Organization introduced the concept of intrinsic capacity (IC), a composite of all the individual-level attributes that contribute to 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.

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Research summary

The study identifies novel genomic loci associated with intrinsic capacity, which is crucial for understanding the genetic basis of healthy aging. This research is relevant as it explores genetic factors that contribute to intrinsic capacity, a composite measure linked to healthy aging, thereby addressing root causes of aging rather than merely treating age-related symptoms.

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