Dataset Information

Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly.

ABSTRACT: The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution.To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans.Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort.Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women.Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.

SUBMITTER: Jacobsson JA

PROVIDER: S-EPMC3103532 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly.

Jacobsson Josefin A JA Almén Markus Sällman MS Benedict Christian C Hedberg Lilia A LA Michaëlsson Karl K Brooks Samantha S Kullberg Joel J Axelsson Tomas T Johansson Lars L Ahlström Håkan H Fredriksson Robert R Lind Lars L Schiöth Helgi B HB

PloS one 20110527 5

<h4>Background</h4>The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution.<h4>Objective</h4>To examine whether the FTO gene is associated with overweight and body compositio ...[more]

PMID: 21637715

Similar Datasets

Project description:BackgroundOlder adults with diabetes take fewer steps per day than those without diabetes. The purpose of the present study was to investigate the association of daily step count with incident diabetes in community-dwelling 70-year-olds.MethodsThis prospective cohort study included N = 3055 community-dwelling 70-year-olds (52% women) who participated in a health examination in Umeå, Sweden during 2012-2017, and who were free from diabetes at baseline. Daily step count was measured for 1 week using Actigraph GT3X+ accelerometers. Cases of diabetes were collected from the Swedish National Patient Register. The dose-response association was evaluated graphically using a flexible parametric model, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regressions.ResultsDuring a mean follow-up of 2.6 years, diabetes was diagnosed in 81 participants. There was an inverse nonlinear dose-response association between daily step count and incident diabetes, with a steep decline in risk of diabetes from a higher daily step count until around 6000 steps/day. From there, the risk decreased at a slower rate until it leveled off at around 8000 steps/day. A threshold of 4500 steps/day was found to best distinguish participants with the lowest risk of diabetes, where those taking ≥ 4500 steps/day, had 59% lower risk of diabetes, compared to those taking fewer steps (HR, 0.41, 95% CI, 0.25-0.66). Adjusting for visceral adipose tissue (VAT) attenuated the association (HR, 0.64, 95% CI, 0.38-1.06), which was marginally altered after further adjusting for sedentary time, education and other cardiometabolic risk factors and diseases (HR, 0.58, 95% CI, 0.32-1.05).ConclusionsA higher daily step count is associated with lower risk of incident diabetes in community-dwelling 70-year-olds. The greatest benefits occur at the lower end of the activity range, and much earlier than 10,000 steps/day. With the limitation of being an observational study, these findings suggest that promoting even a modest increase in daily step count may help to reduce the risk of diabetes in older adults. Because VAT appears to partly mediate the association, lifestyle interventions targeting diabetes should apart from promoting physical activity also aim to prevent and reduce central obesity.

Project description:We investigate associations between normal-appearing white matter microstructural integrity in cognitively normal ∼70-year-olds and concurrently measured brain health and cognition, demographics, genetics and life course cardiovascular health. Participants born in the same week in March 1946 (British 1946 birth cohort) underwent PET-MRI around age 70. Mean standardized normal-appearing white matter integrity metrics (fractional anisotropy, mean diffusivity, neurite density index and orientation dispersion index) were derived from diffusion MRI. Linear regression was used to test associations between normal-appearing white matter metrics and (i) concurrent measures, including whole brain volume, white matter hyperintensity volume, PET amyloid and cognition; (ii) the influence of demographic and genetic predictors, including sex, childhood cognition, education, socio-economic position and genetic risk for Alzheimer's disease (APOE-ɛ4); (iii) systolic and diastolic blood pressure and cardiovascular health (Framingham Heart Study Cardiovascular Risk Score) across adulthood. Sex interactions were tested. Statistical significance included false discovery rate correction (5%). Three hundred and sixty-two participants met inclusion criteria (mean age 70, 49% female). Higher white matter hyperintensity volume was associated with lower fractional anisotropy [b = -0.09 (95% confidence interval: -0.11, -0.06), P < 0.01], neurite density index [b = -0.17 (-0.22, -0.12), P < 0.01] and higher mean diffusivity [b = 0.14 (-0.10, -0.17), P < 0.01]; amyloid (in men) was associated with lower fractional anisotropy [b = -0.04 (-0.08, -0.01), P = 0.03)] and higher mean diffusivity [b = 0.06 (0.01, 0.11), P = 0.02]. Framingham Heart Study Cardiovascular Risk Score in later-life (age 69) was associated with normal-appearing white matter {lower fractional anisotropy [b = -0.06 (-0.09, -0.02) P < 0.01], neurite density index [b = -0.10 (-0.17, -0.03), P < 0.01] and higher mean diffusivity [b = 0.09 (0.04, 0.14), P < 0.01]}. Significant sex interactions (P < 0.05) emerged for midlife cardiovascular health (age 53) and normal-appearing white matter at 70: marginal effect plots demonstrated, in women only, normal-appearing white matter was associated with higher midlife Framingham Heart Study Cardiovascular Risk Score (lower fractional anisotropy and neurite density index), midlife systolic (lower fractional anisotropy, neurite density index and higher mean diffusivity) and diastolic (lower fractional anisotropy and neurite density index) blood pressure and greater blood pressure change between 43 and 53 years (lower fractional anisotropy and neurite density index), independently of white matter hyperintensity volume. In summary, poorer normal-appearing white matter microstructural integrity in ∼70-year-olds was associated with measures of cerebral small vessel disease, amyloid (in males) and later-life cardiovascular health, demonstrating how normal-appearing white matter can provide additional information to overt white matter disease. Our findings further show that greater 'midlife' cardiovascular risk and higher blood pressure were associated with poorer normal-appearing white matter microstructural integrity in females only, suggesting that women's brains may be more susceptible to the effects of midlife blood pressure and cardiovascular health.

Project description:BackgroundBody composition (BC) is an important factor in determining the risk of type 2-diabetes and cardiovascular disease. Computed tomography (CT) is a useful imaging technique for studying BC, however manual segmentation of CT images is time-consuming and subjective. The purpose of this study is to develop and evaluate fully automated segmentation techniques applicable to a 3-slice CT imaging protocol, consisting of single slices at the level of the liver, abdomen, and thigh, allowing detailed analysis of numerous tissues and organs.MethodsThe study used more than 4000 CT subjects acquired from the large-scale SCAPIS and IGT cohort to train and evaluate four convolutional neural network based architectures: ResUNET, UNET++, Ghost-UNET, and the proposed Ghost-UNET++. The segmentation techniques were developed and evaluated for automated segmentation of the liver, spleen, skeletal muscle, bone marrow, cortical bone, and various adipose tissue depots, including visceral (VAT), intraperitoneal (IPAT), retroperitoneal (RPAT), subcutaneous (SAT), deep (DSAT), and superficial SAT (SSAT), as well as intermuscular adipose tissue (IMAT). The models were trained and validated for each target using tenfold cross-validation and test sets.ResultsThe Dice scores on cross validation in SCAPIS were: ResUNET 0.964 (0.909-0.996), UNET++ 0.981 (0.927-0.996), Ghost-UNET 0.961 (0.904-0.991), and Ghost-UNET++ 0.968 (0.910-0.994). All four models showed relatively strong results, however UNET++ had the best performance overall. Ghost-UNET++ performed competitively compared to UNET++ and showed a more computationally efficient approach.ConclusionFully automated segmentation techniques can be successfully applied to a 3-slice CT imaging protocol to analyze multiple tissues and organs related to BC. The overall best performance was achieved by UNET++, against which Ghost-UNET++ showed competitive results based on a more computationally efficient approach. The use of fully automated segmentation methods can reduce analysis time and provide objective results in large-scale studies of BC.

Dataset Information

Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly.

Publications

Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets