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Growth and adult body size trajectories

 

What is the impact on ageing of different trajectories of body size from birth onwards?


Research programme: Growth and body size trajectories in relation to ageing outcomes

Programme Leader: Dr Rebecca Hardy

Investigator scientist: Dr Andrew Wills

PhD students: Rebecca Landy, Zaina al Kanaani

External collaborators:

*                     Professor Scott Hofer, Oregon University

*                     Dr Fiona Matthews, MRC Biostatistics Unit

*                     Professor Debbie Lawlor, MRC CAiTE Centre, University of Bristol

*                     Professor Avan Aihie Sayer, MRC Epidemiology Resource Centre

*                     Ms Michaela Benzeval, MRC Social and Public Health Sciences Unit


Birth weight and childhood growth have been shown in the NSHD and other studies to be related to later morbidity and mortality. For example, low birth weight is associated with higher risk of cardiovascular disease and higher blood pressure, while high birth weight is associated with a higher risk of breast cancer among women. Obesity, or high body mass index, at all ages is major public health problem, with obesity being one of the main risk factors for cardiovascular disease and diabetes.

The overall aim of this research programme is to investigate the impact of childhood growth, pubertal timing and trajectories of adult body size on ageing, and to investigate the life course factors that influence growth and the shape of the adult body size trajectory. The programme also develops life course methodology for analysis of trajectories both as outcome and explanatory variables and for inter-cohort comparisons.  


Objectives

*                     To evaluate how birth weight, growth, age at puberty and the adult BMI trajectory are associated with new clinical measures of cardiovascular and musculoskeletal function and biomarkers of ageing

*                     To assess whether adult lifestyle, particularly physical activity and socioeconomic status, modify the associations of poor early growth and obesity onset with these outcomes

*                     To investigate the environmental, behavioural and genetic factors which influence early growth, obesity onset and BMI throughout life

*                     To develop, apply and compare different statistical models for linking lifetime body size trajectories to ageing outcomes and for inter-cohort research


Sample finding

Investigating how genes influence body size across the life course

Studies have recently identified common genetic variants that are associated with higher body mass index (BMI), a measure of adiposity, in adults. The two strongest common variants were in the FTO gene and near to the MC4R gene. We found important changes in the associations between body size and both genetic variants with age.  Associations strengthened during childhood and adolescence, reaching a peak at age 20 years. The relationships then weakened with increasing adult age. Associations with the FTO gene were most apparent with body mass index, whereas the MC4R gene showed stronger associations with weight, as it was also related with adult height. The experience of post war food rationing in the first years of life may have diminished the influence of genotype in childhood, while weight gain in later adult life may have become increasingly determined or modified by behavioural and environmental influences rather than genotype.

From: Hardy, R, Wills, AK, Wong, A, Elks, CE, Wareham, NJ, Loos, RJF, Kuh, D, Ong, KK. Life course variations in the associations between FTO and MC4R gene variants and body size. Human Molecular Genetics 2010; 19: 545-52

 

Sample finding

Early adult body mass index is associated with premature mortality

Adult body mass index (BMI), a marker of adiposity, has been consistently related to mortality, but little is known about the impact of earlier life BMI on adult mortality. We investigated the impact of childhood, adolescent and early adult BMI on premature adult all cause-mortality. In both men and women, BMI from age 20 years onwards showed a consistent U-shaped relationship with adult mortality with higher mortality rates among those with low and those with high BMI. In females, a similar relationship was observed with adolescent BMI. BMI in childhood (from 2 to 11 years) was generally not associated with adult mortality. The exception was for BMI at age 4 years among women, where a U-shaped relationship was again observed. These findings suggest that promoting a normal “healthy” weight in late adolescence and early adulthood could help prevent premature mortality.

From: Strand, BH, Kuh, D, Shah, I, Guralnik, J, Hardy, R. Childhood, adolescent and early adult body mass index in relation to adult mortality: results from the British 1946 birth cohort. Journal of Epidemiology and Community Health; doi:10.1136/jech.2010-110155.

 

Selected recent programme publications

Strand, BH, Kuh, D, Shah, I, Guralnik, J, Hardy, R. Childhood, adolescent and early adult body mass index in relation to adult mortality: results from the British 1946 birth cohort. Journal of Epidemiology and Community Health; doi:10.1136/jech.2010-110155.

Ong, KK, Elks, CE, Wills, AK, Wong, A, Wareham, NJ, Loos, RJF, Kuh, D, Hardy, R. Timing of associations between polymorphism in LIN28B and BMI across the life course. Journal of Clinical Endocrinology and Metabolism 2011; 96: E125-129.

Gaysina, D, Hotopf, M, Richards, M, Colman, I, Kuh, D, Hardy, R. Symptoms of depression and anxiety, and change in body mass index from adolescence to adulthood: results from a British birth cohort. Psychological Medicine 2011; 41: 175-184.

Cooper, R, Kuh, D, Hardy, R and the Mortality Review Group on behalf of the FALCon and HALCyon study teams. Objective measures of physical capability and subsequent mortality: a systematic review and meta-analysis. British Medical Journal 2010; 341: c4467. doi:10.1136/bmj.c4467.

Cooper, R, Kuh, D, Cooper, C, Gale, C, Lawlor, DA. Matthews, F, Hardy, R, and the FALCon and HALCyon study teams. Objective measures of physical capability and subsequent health: a systematic review of published literature. Age and Ageing 2011;40:14-23.

Pierce, M, Kuh, D, Hardy, R. Role of lifetime body mass index in the association between age at puberty and adult lipids: findings from men and women in a British birth cohort. Annals of Epidemiology 2010; 20: 676-682.

Wills, AK, Hardy, RJ, Black, S, Kuh, D. Trajectories of overweight and body mass index in adulthood and blood pressure at age 53: the 1946 British Birth Cohort study. Journal of Hypertension 2010; 28: 679-686.

Hardy, R, Wills, AK, Wong, A, Elks, CE, Wareham, NJ, Loos, RJF, Kuh, D, Ong, KK. Life course variations in the associations between FTO and MC4R gene variants and body size. Human Molecular Genetics 2010; 19: 545-52

Mishra, G, Nitsch, D, Black, S, De Stavola, BL, Kuh, D, Hardy, R. A structured approach to modelling the effects of binary exposure variables across the life course. International Journal of Epidemiology 2009; 38: 528-537.

Li, L, Hardy, R, Kuh, D, Lo Conte, R, Power, C. Child-to-adult BMI and height trajectories: a comparison of two British birth cohorts. American Journal of Epidemiology 2008; 168: 1008-1015.

Hardy, R, Mishra, GD, Kuh, D. Trajectories of body mass index in relation to age at menopause in a British birth cohort. Maturitas 2008; 59: 304-314.

Skidmore, PM, Hardy, RJ, Kuh, DJ, Langenberg, C, Wadsworth, MEJ. Life course body size and lipid levels at 53 years in a British birth cohort. Journal of Epidemiology and Community Health 2007; 61: 215-20.

Hardy, R, Kuh, D, Whincup, PH, Wadsworth MEJ. Age at puberty and adult blood pressure and body size in a British birth cohort study. Journal of Hypertension 2006; 24:59-66

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