Genetic influence on within-person longitudinal change in anthropometric traits in the UK Biobank

Nat Commun. 2024 May 6;15(1):3776. doi: 10.1038/s41467-024-47802-7.

Abstract

The causes of temporal fluctuations in adult traits are poorly understood. Here, we investigate the genetic determinants of within-person trait variability of 8 repeatedly measured anthropometric traits in 50,117 individuals from the UK Biobank. We found that within-person (non-directional) variability had a SNP-based heritability of 2-5% for height, sitting height, body mass index (BMI) and weight (P 2.4 × 10-3). We also analysed longitudinal trait change and show a loss of both average height and weight beyond about 70 years of age. A variant tracking the Alzheimer's risk APOE- E 4 allele (rs429358) was significantly associated with weight loss ( β = -0.047 kg per yr, s.e. 0.007, P = 2.2 × 10-11), and using 2-sample Mendelian Randomisation we detected a relationship consistent with causality between decreased lumbar spine bone mineral density and height loss (bxy = 0.011, s.e. 0.003, P = 3.5 × 10-4). Finally, population-level variance quantitative trait loci (vQTL) were consistent with within-person variability for several traits, indicating an overlap between trait variability assessed at the population or individual level. Our findings help elucidate the genetic influence on trait-change within an individual and highlight disease risks associated with these changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Alzheimer Disease / genetics
  • Anthropometry
  • Apolipoproteins E* / genetics
  • Body Height* / genetics
  • Body Mass Index*
  • Body Weight / genetics
  • Bone Density / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Longitudinal Studies
  • Lumbar Vertebrae
  • Male
  • Mendelian Randomization Analysis
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • UK Biobank
  • United Kingdom

Substances

  • Apolipoproteins E