Using linear and natural cubic splines, SITAR, and latent trajectory models to characterise nonlinear longitudinal growth trajectories in cohort studies

BMC Medical Research Methodology - Tập 22 - Trang 1-20 - 2022
Ahmed Elhakeem1,2, Rachael A. Hughes1,2, Kate Tilling1, Diana L. Cousminer3,4,5, Stefan A. Jackowski6,7, Tim J. Cole8, Alex S. F. Kwong1,2,9, Zheyuan Li10,11, Struan F. A. Grant3,4,5,12,13, Adam D. G. Baxter-Jones6, Babette S. Zemel12,14, Deborah A. Lawlor1,2
1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
2Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
3Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, USA
4Department of Genetics, University of Pennsylvania, Philadelphia, USA
5Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, USA
6College of Kinesiology , University of Saskatchewan , Saskatoon , Canada
7Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada
8UCL Great Ormond Street Institute of Child Health, London, UK
9Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
10School of Mathematics and Statistics, Henan University, Kaifeng, China
11Department of Statistics and Actuarial Sciences, Simon Fraser University, Burnaby, Canada
12Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
13Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, USA
14Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, USA

Tóm tắt

Longitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. Our aim was to provide an accessible guide along with applied examples to using four sophisticated modelling procedures for describing nonlinear growth trajectories. This expository paper provides an illustrative guide to summarising nonlinear growth trajectories for repeatedly measured continuous outcomes using (i) linear spline and (ii) natural cubic spline linear mixed-effects (LME) models, (iii) Super Imposition by Translation and Rotation (SITAR) nonlinear mixed effects models, and (iv) latent trajectory models. The underlying model for each approach, their similarities and differences, and their advantages and disadvantages are described. Their application and correct interpretation of their results is illustrated by analysing repeated bone mass measures to characterise bone growth patterns and their sex differences in three cohort studies from the UK, USA, and Canada comprising 8500 individuals and 37,000 measurements from ages 5–40 years. Recommendations for choosing a modelling approach are provided along with a discussion and signposting on further modelling extensions for analysing trajectory exposures and outcomes, and multiple cohorts. Linear and natural cubic spline LME models and SITAR provided similar summary of the mean bone growth trajectory and growth velocity, and the sex differences in growth patterns. Growth velocity (in grams/year) peaked during adolescence, and peaked earlier in females than males e.g., mean age at peak bone mineral content accrual from multicohort SITAR models was 12.2 years in females and 13.9 years in males. Latent trajectory models (with trajectory shapes estimated using a natural cubic spline) identified up to four subgroups of individuals with distinct trajectories throughout adolescence. LME models with linear and natural cubic splines, SITAR, and latent trajectory models are useful for describing nonlinear growth trajectories, and these methods can be adapted for other complex traits. Choice of method depends on the research aims, complexity of the trajectory, and available data. Scripts and synthetic datasets are provided for readers to replicate trajectory modelling and visualisation using the R statistical computing software.

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