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

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 <math xmlns="http://www.w3.org/1998/Math/MathML"><mo>≤</mo></math> 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- <math xmlns="http://www.w3.org/1998/Math/MathML"><mi>E</mi> <mn>4</mn></math> allele (rs429358) was significantly associated with weight loss ( <math xmlns="http://www.w3.org/1998/Math/MathML"><mi>β</mi></math>  = -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 (b_xy = 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.