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Physical activity modifies genetic susceptibility to obesity in postmenopausal women.

ABSTRACT: OBJECTIVE:We conducted a gene-environment interaction study to evaluate whether the association of body mass index (BMI) associated meta genome-wide association study single-nucleotide polymorphisms (SNPs) (as a genetic risk score) and BMI is modified by physical activity and age. METHODS:In 8,206 women of European ancestry from the Women's Health Initiative (WHI), we used linear regression to examine main effects of the 95 SNP BMI genetic risk score (GRS) and physical activity on BMI, and evaluated whether genetic associations are modified by physical activity (two-way interaction) and age (three-way interaction). RESULTS:We found evidence for modification of the BMI GRS-BMI association according to both physical activity and age. We observed a significant two-way interaction of BMI GRS?×?physical activity in the crude model (P interaction?=?0.05), where a smaller effect of the BMI GRS on BMI with increasing physical activity. The beta coefficient was 0.05 (standard error [SE]?=?0.02, P?=?0.01) for the high-activity group compared with beta?=?0.13 (SE?=?0.02, P?=?4.8?×?10) for the sedentary group. The three-way interaction was statistically significant (adjusted P interaction?=?0.01). Notably, in the 70+ age group, the BMI GRS-BMI association was attenuated and no longer significant in the high-activity group; the beta coefficient for the 70+ high-activity group was relatively small and nonsignificant (beta?=?0.02, SE?=?0.03, P?=?0.58) compared with 70+ sedentary group (beta?=?0.17, SE?=?0.03, P?=?2.5?×?10). CONCLUSION:Our study suggests that physical activity attenuates the influence of genetic predisposition to obesity, and this effect is more profound in the oldest age group.

SUBMITTER: Ochs-Balcom HM

PROVIDER: S-EPMC6136965 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Physical activity modifies genetic susceptibility to obesity in postmenopausal women.

Ochs-Balcom Heather M HM Preus Leah L Nie Jing J Wactawski-Wende Jean J Agyemang Linda L Neuhouser Marian L ML Tinker Lesley L Zheng Cheng C Kazlauskaite Rasa R Qi Lihong L Sucheston-Campbell Lara E LE

Menopause (New York, N.Y.) 20181001 10

<h4>Objective</h4>We conducted a gene-environment interaction study to evaluate whether the association of body mass index (BMI) associated meta genome-wide association study single-nucleotide polymorphisms (SNPs) (as a genetic risk score) and BMI is modified by physical activity and age.<h4>Methods</h4>In 8,206 women of European ancestry from the Women's Health Initiative (WHI), we used linear regression to examine main effects of the 95 SNP BMI genetic risk score (GRS) and physical activity on ...[more]

PMID: 29762199

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Project description:BACKGROUND:Maintenance of lean muscle mass and related strength is associated with lower risk for numerous chronic diseases of aging in women. OBJECTIVE:Our aim was to evaluate whether the association between dietary protein and lean mass differs by physical activity level, amino acid composition, and body mass index categories. DESIGN:We performed a cross-sectional analysis of a prospective cohort. PARTICIPANTS/SETTING:Participants were postmenopausal women from the Women's Health Initiative with body composition measurements by dual-energy x-ray absorptiometry (n=8,298). MAIN OUTCOME MEASURES:Our study measured percent lean mass, percent fat mass, and lean body mass index. STATISTICAL ANALYSES PERFORMED:Linear regression models adjusted for scanner serial number, age, calibrated energy intake, race/ethnicity, neighborhood socioeconomic status, and recreational physical activity were used to determine the relationship between protein intake and body composition measures. Likelihood ratio tests and stratified analysis were used to investigate physical activity and body mass index as potential effect modifiers. RESULTS:Biomarker-calibrated protein intake was positively associated with percent lean mass; women in the highest protein quintile had 6.3 percentage points higher lean mass than the lowest quintile (P<0.001). This difference rose to 8.5 percentage points for physically active women in the highest protein quintile (Pinteraction=0.023). Percent fat mass and lean body mass index were both inversely related to protein intake (both P<0.001). Physical activity further reduced percent fat mass (Pinteraction=0.022) and lean body mass index (Pinteraction=0.011). Leucine intake was associated with lean mass, as were branched chain amino acids combined (both P<0.001), but not independent of total protein. All associations were observed for normal-weight, overweight, and obese women. CONCLUSIONS:Protein consumption up to 2.02 g/kg body weight daily is positively associated with lean mass in postmenopausal women. Importantly, those that also engage in physical activity have the highest lean mass across body mass index categories.

Project description:ObjectivesThis study prospectively examined physical activity levels and the incidence of heart failure (HF) in 137,303 women, ages 50 to 79 years, and examined a subset of 35,272 women who, it was determined, had HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF).BackgroundThe role of physical activity in HF risk among older women is unclear, particularly for incidence of HFpEF or HFrEF.MethodsWomen were free of HF and reported ability to walk at least 1 block without assistance at baseline. Recreational physical activity was self-reported. The study documented 2,523 cases of total HF, and 451 and 734 cases of HFrEF and HFpEF, respectively, during a mean 14-year follow-up.ResultsAfter controlling for age, race, education, income, smoking, alcohol, hormone therapy, and hysterectomy status, compared with women who reported no physical activity (reference group), inverse associations were observed across incremental tertiles of total physical activity for overall HF (hazard ratio [HR]: Tertile 1 = 0.89, Tertile 2 = 0.74, Tertile 3 = 0.65; trend p < 0.001), HFpEF (HR: 0.93, 0.70, 0.68; p < 0.001), and HFrEF (HR: 0.81, 0.59, 0.68; p = 0.01). Additional controlling for potential mediating factors included attenuated time-varying coronary heart disease (CHD) (nonfatal myocardial infarction, coronary revascularization) diagnosis but did not eliminate the inverse associations. Walking, the most common form of physical activity in older women, was also inversely associated with HF risks (overall: 1.00, 0.98, 0.93, 0.72; p < 0.001; HFpEF: 1.00, 0.98, 0.87, 0.67; p < 0.001; HFrEF: 1.00, 0.75, 0.78, 0.67; p = 0.01). Associations between total physical activity and HF were consistent across subgroups, defined by age, body mass index, diabetes, hypertension, physical function, and CHD diagnosis. Analysis of physical activity as a time-varying exposure yielded findings comparable to those of baseline physical activity.ConclusionsHigher levels of recreational physical activity, including walking, are associated with significantly reduced HF risk in community-dwelling older women.

Project description:Importance:Physical activity is inversely associated with hip fracture risk in older women. However, the association of physical activity with fracture at other sites and the role of sedentary behavior remain unclear. Objective:To assess the associations of physical activity and sedentary behavior with fracture incidence among postmenopausal women. Design, Setting, and Participants:The Women's Health Initiative prospective cohort study enrolled 77 206 postmenopausal women aged 50 to 79 years between October 1993 and December 1998 at 40 US clinical centers. Participants were observed for outcomes through September 2015, with data analysis conducted from June 2017 to August 2019. Exposures:Self-reported physical activity and sedentary time. Main Outcomes and Measures:Hazard ratios (HRs) and 95% CIs for total and site-specific fracture incidence. Results:During a mean (SD) follow-up period of 14.0 (5.2) years among 77 206 women (mean [SD] age, 63.4 [7.3] years; 66 072 [85.6%] white), 25 516 (33.1%) reported a first incident fracture. Total physical activity was inversely associated with the multivariable-adjusted risk of hip fracture (>17.7 metabolic equivalent [MET] h/wk vs none: HR, 0.82; 95% CI, 0.72-0.95; P for trend < .001). Inverse associations with hip fracture were also observed for walking (>7.5 MET h/wk vs none: HR, 0.88; 95% CI, 0.78-0.98; P for trend = .01), mild activity (HR, 0.82; 95% CI, 0.73-0.93; P for trend = .003), moderate to vigorous activity (HR, 0.88; 95% CI, 0.81-0.96; P for trend = .002), and yard work (HR, 0.90; 95% CI, 0.82-0.99; P for trend = .04). Total activity was positively associated with knee fracture (>17.7 MET h/wk vs none: HR, 1.26; 95% CI, 1.05-1.50; P for trend = .08). Mild activity was associated with lower risks of clinical vertebral fracture (HR, 0.87; 95% CI, 0.78-0.96; P for trend = .006) and total fractures (HR, 0.91; 95% CI, 0.87-0.94; P for trend < .001). Moderate to vigorous activity was positively associated with wrist or forearm fracture (HR, 1.09; 95% CI, 1.03-1.15; P for trend = .004). After controlling for covariates and total physical activity, sedentary time was positively associated with total fracture risk (>9.5 h/d vs <6.5 h/d: HR, 1.04; 95% CI, 1.01-1.07; P for trend = .01). When analyzed jointly, higher total activity mitigated some of the total fracture risk associated with sedentary behavior. Analysis of time-varying exposures resulted in somewhat stronger associations for total physical activity, whereas those for sedentary time were materially unchanged. Conclusions and Relevance:In older ambulatory women, higher total physical activity was associated with lower total and hip fracture risk but higher knee fracture risk. Mild activity and walking were associated with lower hip fracture risk, a finding with important public health implications because these activities are common in older adults. The positive association between sedentary time and total fracture risk requires further investigation.

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Physical activity modifies genetic susceptibility to obesity in postmenopausal women.

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Physical activity modifies genetic susceptibility to obesity in postmenopausal women.

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