The genetic architecture of changes in adiposity during adulthood

Venkatesh, Samvida S.; Ganjgahi, Habib; Palmer, Duncan S.; Coley, Kayesha; Wittemans, Laura B. L.; Nellåker, Christoffer; Holmes, Connor; Lindgren, Cecilia M.; Nicholson, George

doi:10.1101/2023.01.09.23284364

Cited by 2 publications

(1 citation statement)

References 128 publications

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“…The vast majority of GWAS have concentrated on cross-sectional phenotypes (i.e., one measure per person per study). However, many human traits change over time, and there may be a genetic component underlying this dynamic process of change in the trait (see for example, E. N. Smith et al 2010; Warrington et al 2015; A. D. Smith et al 2016; Gouveia et al 2019; 2021; Wendel et al 2021; Venkatesh et al 2023). Therefore, studying trait trajectories is increasingly important to uncover novel loci beyond those found from GWAS of cross-sectional traits.…”

Section: Introductionmentioning

confidence: 99%

A framework for conducting time-varying genome-wide association studies: An application to body mass index across childhood in six multiethnic cohorts

Burrows,

Heiskala,

Bradfield

et al. 2024

Preprint

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Genetic effects on changes in human traits over time are understudied and may have important pathophysiological impact. We propose a framework that enables data quality control, implements mixed models to evaluate trajectories of change in traits, and estimates phenotypes to identify age-varying genetic effects in genome-wide association studies (GWASs). Using childhood body mass index (BMI) as an example, we included 71,336 participants from six cohorts and estimated the slope and area under the BMI curve within four time periods (infancy, early childhood, late childhood and adolescence) for each participant, in addition to the age and BMI at the adiposity peak and the adiposity rebound. GWAS on each of the estimated phenotypes identified 28 genome-wide significant variants at 13 loci across the 12 estimated phenotypes, one of which was novel (in DAOA) and had not been previously associated with childhood or adult BMI. Genetic studies of changes in human traits over time could uncover novel biological mechanisms influencing quantitative traits.

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Section: Introductionmentioning

confidence: 99%

A framework for conducting time-varying genome-wide association studies: An application to body mass index across childhood in six multiethnic cohorts

Burrows,

Heiskala,

Bradfield

et al. 2024

Preprint

View full text Add to dashboard Cite

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

Kemper,

Sidorenko,

Wang

et al. 2024

Nat Commun

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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 × 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-$${{{{{\mathcal{E}}}}}}4$$ 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.

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The genetic architecture of changes in adiposity during adulthood

Cited by 2 publications

References 128 publications

A framework for conducting time-varying genome-wide association studies: An application to body mass index across childhood in six multiethnic cohorts

A framework for conducting time-varying genome-wide association studies: An application to body mass index across childhood in six multiethnic cohorts

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

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