Dataset Information

Life course variations in the associations between FTO and MC4R gene variants and body size.

ABSTRACT: The timing of associations between common genetic variants for weight or body mass index (BMI) across the life course may provide insights into the aetiology of obesity. We genotyped variants in FTO (rs9939609) and near MC4R (rs17782313) in 1240 men and 1239 women born in 1946 and participating in the MRC National Survey of Health and Development. Birth weight was recorded and height and weight were measured or self-reported repeatedly at 11 time-points between ages 2 and 53 years. Hierarchical mixed models were used to test whether genetic associations with weight or BMI standard deviation scores (SDS) changed with age during childhood and adolescence (2-20 years) or adulthood (20-53 years). The association between FTO rs9939609 and BMI SDS strengthened during childhood and adolescence (rate of change: 0.007 SDS/A-allele/year; 95% CI: 0.003-0.010, P < 0.001), reached a peak strength at age 20 years (0.13 SDS/A-allele, 0.08-0.19), and then weakened during adulthood (-0.003 SDS/A-allele/year, -0.005 to -0.001, P = 0.001). MC4R rs17782313 showed stronger associations with weight than BMI; its association with weight strengthened during childhood and adolescence (0.005 SDS/C-allele/year; 0.001-0.008, P = 0.006), peaked at age 20 years (0.13 SDS/C-allele, 0.07-0.18), and weakened during adulthood (-0.002 SDS/C-allele/year, -0.004 to 0.000, P = 0.05). In conclusion, genetic variants in FTO and MC4R showed similar biphasic changes in their associations with BMI and weight, respectively, strengthening during childhood up to age 20 years and then weakening with increasing adult age. Studies of the aetiology of obesity spanning different age groups may identify age-specific determinants of weight gain.

SUBMITTER: Hardy R

PROVIDER: S-EPMC2798720 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Life course variations in the associations between FTO and MC4R gene variants and body size.

Hardy Rebecca R Wills Andrew K AK Wong Andrew A Elks Cathy E CE Wareham Nicholas J NJ Loos Ruth J F RJ Kuh Diana D Ong Ken K KK

Human molecular genetics 20091031 3

The timing of associations between common genetic variants for weight or body mass index (BMI) across the life course may provide insights into the aetiology of obesity. We genotyped variants in FTO (rs9939609) and near MC4R (rs17782313) in 1240 men and 1239 women born in 1946 and participating in the MRC National Survey of Health and Development. Birth weight was recorded and height and weight were measured or self-reported repeatedly at 11 time-points between ages 2 and 53 years. Hierarchical ...[more]

PMID: 19880856

Similar Datasets

Project description:Mammographic density (MD) is a strong risk factor for breast cancer, but the biological mechanism underlying this association is not clear. Current adult body mass index (BMI) is inversely associated with percent MD; however, few studies have included Hispanic women or evaluated associations with measures of body fatness earlier in life. ESMaestras was established in 2006, when 28,345 women ages ?35 responded to a detailed questionnaire that assessed possible disease risk factors, including body fatness in childhood, adolescence, and young adulthood. In 2007, 2084 ESMaestras participants underwent a clinical examination, which included measurements of weight, height, and sitting height and a mammogram. We measured percent MD using a computer-assisted method. The current analysis includes 972 premenopausal and 559 postmenopausal women. We used multivariable linear regression to evaluate associations between measures of body size and MD, independent of current BMI. Among pre- and postmenopausal women, we observed no significant associations between body fatness during childhood, adolescence, or young adulthood and percent MD. Among postmenopausal women, we observed a modest positive association between body fatness immediately before first pregnancy and between ages 25 and 35 after adjustment for current BMI, with differences of 4.9 and 3.6 % points, respectively, in percent MD between the heaviest and leanest women (p-trend = 0.02). There were no significant associations between height, sitting height, and percent MD among pre- or postmenopausal women in multivariable models adjusting for BMI. In general, we found no clear associations between measures of body size in early life, current sitting height, or current height, and percent MD, after adjusting for current BMI, in this population of Mexican women. Our observation of a positive association between early adult body fatness (i.e., before first pregnancy and ages 25-35) and percent MD among postmenopausal women is inconsistent with prior research and requires confirmation in other studies.

Dataset Information

Life course variations in the associations between FTO and MC4R gene variants and body size.

Publications

Life course variations in the associations between FTO and MC4R gene variants and body size.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets