| Title: | The genetic architecture of biological age in nine human organ systems |
| Journal: | Nature Aging |
| Published: | 28 Jun 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38942983/ |
| DOI: | https://doi.org/10.1038/s43587-024-00662-8 |
| URL: | https://www.medrxiv.org/content/medrxiv/early/2023/06/17/2023.06.08.23291168.full.pdf |
| Citations: | 2 (2 in last 2 years) as of 8 Aug 2024 |
Publication 11769
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Abstract
Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chronological age) across nine human organ systems in 377,028 participants of European ancestry from the UK Biobank. The BAGs were computed using cross-validated support vector machines, incorporating imaging, physical traits and physiological measures. We identify 393 genomic loci-BAG pairs (P < 5 × 10-8) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary and renal systems. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system (organ specificity) while exerting pleiotropic links with other organ systems (interorgan cross-talk). We find that genetic correlation between the nine BAGs mirrors their phenotypic correlation. Further, a multiorgan causal network established from two-sample Mendelian randomization and latent causal variance models revealed potential causality between chronic diseases (for example, Alzheimer's disease and diabetes), modifiable lifestyle factors (for example, sleep duration and body weight) and multiple BAGs. Our results illustrate the potential for improving human organ health via a multiorgan network, including lifestyle interventions and drug repurposing strategies.</p>
10 Keywords
- Aged
- Aging
- Female
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Organ Specificity
- Phenotype
- United Kingdom
11 Authors
- Junhao Wen
- Ye Ella Tian
- Ioanna Skampardoni
- Zhijian Yang
- Yuhan Cui
- Filippos Anagnostakis
- Elizabeth Mamourian
- Bingxin Zhao
- Arthur W. Toga
- Andrew Zalesky
- Christos Davatzikos
Enabling scientific discoveries that improve human health