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Kemper, Kathryn E; Sidorenko, Julia; Wang, Huanwei; Hayes, Ben J; Wray, Naomi R; Yengo, Loic; Keller, Matthew C; Goddard, Michael; Visscher, Peter M
Nature communications, 05/2024, Letnik: 15, Številka: 1Journal Article
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 ). 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- allele (rs429358) was significantly associated with weight loss ( = -0.047 kg per yr, s.e. 0.007, P = 2.2 × 10 ), and using 2-sample Mendelian Randomisation we detected a relationship consistent with causality between decreased lumbar spine bone mineral density and height loss (b = 0.011, s.e. 0.003, P = 3.5 × 10 ). 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.
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