| Title: | Height variation independent of known genetic variants and health in later life: a cohort study |
| Journal: | American Journal of Clinical Nutrition |
| Published: | 1 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42386083/ |
| DOI: | https://doi.org/10.1016/j.ajcnut.2026.101425 |
Publication 20481
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Abstract
BACKGROUND: Adult-attained height is associated with later-life health, but it reflects both genetic and non-genetic influences. The health implications of height variation not explained by known common height-associated genetic variants remain unclear.</p>
OBJECTIVE: To examine associations of residual height (height variation independent of known genetic variants) with multiple disease incidence and all-cause mortality in later life.</p>
METHODS: In this cohort study of 407,366 adults of European ancestry (aged 40-70) in UK Biobank (2006-2010), sex- and age-specific genetically predicted height was estimated from 9,863 height-associated variants, adjusted for 30 principal components of ancestry. Residual height was calculated as the difference between observed and genetically predicted height. Plasma proteomics (2,054 proteins; OlinkTM Explore) were profiled. Deaths and 49 incident diseases were ascertained through national registries. Multivariable Cox models estimated associations of residual height and related proteins with disease incidence and mortality.</p>
RESULTS: Higher residual height (mean [SD], 0.0 [4.8]) was associated with more favorable self-reported pre-adulthood exposures (e.g., later birth years, no maternal smoking around birth, being breastfed as a baby, no adoption experience, and lower childhood adversity scores) and lower hazard ratios of 32 out of 49 diseases (median follow-up=∼12.5 years). Using participants with residual height within ±0.5 SDs from the mean as reference, those with residual height <-2 SDs had higher adjusted hazard ratios of mortality (1.61; 95% confidence interval 1.50, 1.72), multimorbidity (1.28; 1.12, 1.46), cardiovascular disease (1.45; 1.32, 1.60), psychiatric/neurological disease (1.38; 1.28, 1.48), and other disease categories (e.g., diabetes, digestive, and musculoskeletal diseases). In contrast, higher genetically predicted height was associated with higher incidence of 19 diseases, including subtypes of cancer, non-atherosclerotic cardiovascular diseases, and musculoskeletal diseases, as well as higher all-cause mortality. We identified 806 plasma proteins related to inflammation, immune response, and autophagy via TNF, NF-κB, PI3K-Akt, and JAK-STAT signaling pathways, which were associated with residual height and multiple diseases and mortality.</p>
CONCLUSION: Higher residual height was associated with lower disease incidence and mortality, with associations distinct from those for genetically predicted height.</p>
10 Authors
- Yanbo Zhang
- Yang Li
- Xiaonan Xue
- Tao Wang
- Jee-Young Moon
- Carmen R Isasi
- Bing Yu
- Thomas E Rohan
- Robert C Kaplan
- Qibin Qi
1 Application
| Application ID | Title |
|---|---|
| 56483 | Diet, metabolic/inflammatory profile and risk of obesity-related chronic conditions among participants in the UK Biobank |
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