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

  • Kathryn E. Kemper,
  • Julia Sidorenko,
  • Huanwei Wang,
  • Ben J. Hayes,
  • Naomi R. Wray,
  • Loic Yengo,
  • Matthew C. Keller,
  • Michael Goddard,
  • Peter M. Visscher

摘要

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 \(\le\) 2.4 × 103). 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- \({{{{{\mathcal{E}}}}}}4\) E 4 allele (rs429358) was significantly associated with weight loss ( \(\beta\) 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.