Genetic variants and physical activity interact to affect bone density in Hispanic children

Abstract Background Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study. Methods Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine BMD. Results We found evidence of statistically significant interaction effects between the PRS and MVPA on total body BMD and lumbar spine BMD (p < 0.05). Higher PRS was associated with a lower total body BMD (β = − 0.040 ± 0.009, p = 1.1 × 10− 5) and lumbar spine BMD (β = − 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (β = − 0.015 ± 0.006, p = 0.02; β = 0.008 ± 0.01, p = 0.4, respectively). Discussion The study indicated that calcium intake does not modify the relationship between genetic variants and BMD, while it implied physical activity interacts with genetic variants to affect BMD in Hispanic children. Due to limited sample size of our study, future research on gene by environment interaction on bone health and functional studies to provide biological insights are needed. Conclusions Bone health in Hispanic children with high genetic risk for low BMD is benefitted more by MVPA than children with low genetic risk. Our results may be useful to predict disease risk and tailor dietary and physical activity advice delivery to people, especially children.

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Interaction between physical activity and polygenic risk score for type-2 diabetes in older Americans

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.888 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

Y Y Wu ◽

M D Thompson ◽

F Youkhana ◽

C M Pirkle

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Genetic Risk ◽

Significant Interaction ◽

The United States ◽

Lifestyle Factors ◽

Polygenic Risk Score ◽

Environment Interaction ◽

Polygenic Risk

Abstract Background Genetics plays an important role in the development of type-2 diabetes (T2D). Polygenic risk scores (PRS) are increasingly used to quantify genetic risk of T2D in epidemiological studies. These scores, when integrated into analyses of modifiable lifestyle factors, may improve understanding of T2D etiology, as the strength of association with T2D and some lifestyle or demographic factors may vary according to genetic predisposition. Methods We examined PRS-lifestyle factor interactions on T2D with data from the United States Health and Retirement Study (HRS), a prospective longitudinal cohort of older adults (≥50 at baseline). HRS contains nationally representative samples of Black and White Americans with pre-calculated PRS for T2D (N = 14,001). Covariates included sex, education, BMI, smoking, alcohol, and physical activity. Predicted prevalence and incidence of T2D were calculated with logistic regression models. Nonparametric bootstrap method was performed to calculate differences in T2D prevalence and incidence by PRS percentiles and interaction variables. Results Significant interaction (p_interaction=0.0096) was detected between PRS and physical activity among Whites only. In those with the lowest decile of PRS, T2D prevalence was similar (∼10%) for those reporting no physical activity compared to low or moderate activity. In those with the top decile of PRS, lower T2D prevalence (17%, 95%CI:14.8,19.6) was observed among those with moderate compared to no activity (24%, 95%CI:20.4,27.5). Incident T2D in Whites followed a similar pattern (p_interaction=0.0194). Among Black participants, no significant interaction with any lifestyle variables was detected. Conclusions Interaction of different genetic risk profiles with lifestyle factors may inform understanding of why certain inventions are more or less effective in different groups of people, potentially improving clinical and prevention interventions. Key messages Protection conferred by physical activity on T2D varied by underlying genetic risk. Gene-environment interaction studies provide insights on why lifestyle factors vary in their associations with T2D.

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Sodium Intake and Osteoporosis. Findings From the Women's Health Initiative

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-4017 ◽

2016 ◽

Vol 101 (4) ◽

pp. 1414-1421 ◽

Cited By ~ 11

Author(s):

Laura Carbone ◽

Karen C. Johnson ◽

Ying Huang ◽

Mary Pettinger ◽

Fridjtof Thomas ◽

...

Keyword(s):

Lumbar Spine ◽

Women's Health ◽

Postmenopausal Women ◽

Calcium Intake ◽

Sodium Intake ◽

Women's Health Initiative ◽

Health Initiative ◽

Skeletal Site ◽

Total Body ◽

The Women’S Health Initiative

Abstract Background: The relationship of sodium intake to changes in bone mineral density (BMD) in postmenopausal women has not been established, and no study to date has examined its relationship with fracture risk. Methods: This was a prospective observational cohort study including 69 735 postmenopausal women in the Women's Health Initiative during an average of 11.4 years of followup to examine whether sodium intake is associated with changes in BMD at the lumbar spine, total hip, femoral neck, and total body and with incident fractures and whether this relationship is modified by potassium and/or calcium intake. Results: In adjusted models, there was no association of calibrated sodium intake with changes in BMD at the hip or lumbar spine from baseline to 3 or 6 years (P ≥ .06). Higher sodium intakes were associated with greater increases in total body BMD from baseline to 3 years (P = .00) with a trend from baseline to 6 years (P = .08) and with reduced hip fractures (hazard ratio, 0.81; 95% confidence interval, 0.67–0.97). In sensitivity analyses that included body mass index as an additional covariate in the models, there was no association of sodium intake with changes in BMD at any skeletal site (P ≥ .32) or with incident fractures (P > .28). There was no association of sodium intake with incident fractures after adjusting for potassium intake (P ≥ .30). Calcium intake did not modify the association between sodium intake and incident fractures (P ≥ .20). Levels of sodium intake above or below currently recommended guidelines for cardiovascular disease (≤ 2300 mg/d) were not associated with changes in BMD at any skeletal site from baseline to 3 (P ≥ .66) or 6 years (P ≥ .74) or with incident fractures (P ≥ .70). Conclusion: Current population-based recommendations for sodium intake are unlikely to significantly affect osteoporosis.

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Subcutaneous fat mass is associated with genetic risk scores related to proinflammatory cytokine signaling and interact with physical activity in middle-aged obese adults

Nutrition & Metabolism ◽

10.1186/s12986-019-0405-0 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 1

Author(s):

James W. Daily ◽

Hye Jeong Yang ◽

Meiling Liu ◽

Min Jung Kim ◽

Sunmin Park

Keyword(s):

Physical Activity ◽

Fat Mass ◽

Visceral Fat ◽

Genetic Variants ◽

Genetic Risk ◽

Odds Ratio ◽

Subcutaneous Fat ◽

Risk Scores ◽

Obese Adults ◽

High Physical Activity

Abstract Background and aims Subcutaneous fat mass is negatively correlated with atherogenic risk factors, but its putative benefits remain controversial. We hypothesized that genetic variants that influence subcutaneous fat mass would modulate lipid and glucose metabolism and have interactions with lifestyles in Korean middle-aged adults with high visceral fat. Materials and methods Subcutaneous fat mass was categorized by dividing the average of subscapular skin-fold thickness by BMI and its cutoff point was 1.2. Waist circumferences were used for representing visceral fat mass with Asian cutoff points. GWAS of subjects aged 40–65 years with high visceral fat (n = 3303) were conducted and the best gene-gene interactions from the genetic variants related to subcutaneous fat were selected and explored using the generalized multifactor dimensionality reduction. Genetic risk scores (GRS) were calculated by weighted GRS that was divided into low, medium and high groups. Results Subjects with high subcutaneous fat did not have dyslipidemia compared with those with low subcutaneous fat, although both subject groups had similar amounts of total fat. The best model to influence subcutaneous fat included IL17A_rs4711998, ADCY2_rs326149, ESRRG_rs4846514, CYFIP2_rs733730, TCF7L2_rs7917983, ZNF766_rs41497444 and TGFBR3_rs7526590. The odds ratio (OR) for increasing subcutaneous fat was higher by 2.232 folds in the high-GRS group, after adjusting for covariates. However, total and LDL cholesterol, triglyceride and C-reactive protein concentrations in the circulation were not associated with GRS. Subjects with high-GRS had higher serum HDL cholesterol levels than those with low-GRS. Physical activity and GRS had an interaction with subcutaneous fat. In subjects with low physical activity, the odds ratio for high subcutaneous fat increased by 2.232, but subcutaneous fat deposition was not affected in the high-GRS group with high physical activity. Conclusion Obese adults with high-GRS had more subcutaneous fat, but they did not show more dyslipidemia and inflammation compared to low-GRS. High physical activity prevented subcutaneous fat deposition in subjects with high GRS for subcutaneous fat.

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Body Composition and Its Relationship to Growth and Bone Mass in Patients with Thalassemia

Blood ◽

10.1182/blood.v112.11.3890.3890 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3890-3890

Author(s):

Ellen Fung ◽

Yan Xu ◽

Janet Kwiatkowski ◽

Sylvia Titi Singer ◽

Ashutosh Lal ◽

...

Keyword(s):

Physical Activity ◽

Body Composition ◽

Nutritional Status ◽

Bone Mass ◽

Body Fat ◽

Lean Mass ◽

Bone Health ◽

Calcium Intake ◽

Z Score ◽

Percentage Body Fat

Abstract Optimal nutritional status is imperative for achieving the genetic potential for growth and development in children as well as for robust immune function and bone health in adults. Patients with thalassemia (Thal) are known to have abnormal growth, altered development and immune function and deficits in bone mass. For children, weight and height is commonly used to assess overall nutritional status, whereas for adults, body composition is a gross marker of an individual’s overall nutritional health. Nutritional status and body composition has not been explored in patients with Thal. To examine this, we have assessed body composition (fat, lean) and bone density by dual energy x-ray absorptiometry (DXA, Hologic Delphi A) in 370 subjects enrolled in a cross-sectional study of the Thal Clinical Research Network (TCRN), a North American collaborative research group. In addition to DXA, weight and height were measured, medical history obtained and a brief calcium food frequency and physical activity questionnaire completed. The total sample was divided into 2 groups: (TxThal) 257 transfused thalassemia major and E-beta thal patients (23.7 ± 11 yr, 131 male), and (NTxThal) 113 never or minimally transfused patients with other thalassemia syndromes (21.3 ± 13 yr, 50 male). Body mass index (BMI) was calculated (kg/m2) and cutoffs determined for children (<17=underweight, ≥30 obese) and adults (<18.5=underweight, ≥30 obese). As expected there was a high correlation between BMI and fat and lean mass by DXA (r=0.7 to 0.86, p<0.001). 6.2% of adults and 39.3% of children were classified as underweight by BMI and nearly 1/3 of children with Thal had abnormally low percentage body fat; while only 3.4% of adults and 2.2% of children were considered obese. Compared to median data from NHANES, adult patients with Thal are much leaner (BMI: 22.8±0.4) compared to contemporary adult Americans (28.1±0.2, p<0.0001). TxThal had more total body fat mass (14.3 vs 11.4 g, p<0.0001) and percentage body fat (27.3% vs. 24.9% p=0.007) compared to NTxThal. As has been observed in epidemiological studies of healthy subjects, calcium intake was inversely related to fat mass (p=0.009) as well as lean mass (p=0.007) after controlling for the effects of age, gender and diagnosis. Current physical activity level was a strong predictor of reduced body fat (p=0.007), whereas hemoglobin level was positively related to lean mass (p=0.001). Moreover, body fat was a positive predictor for height Z-score (p<0.0001). Low bone mass (BMD Z-Score <−2.0) was found in 50% of subjects, and BMD Z-score was moderately correlated with height Z-score (p<0.0001) and weight Z-score (p<0.0001). Though the majority of patients with Thal were classified as having a healthy body composition with very few obese patients, nearly 40% of the children in this sample were underweight. NTxThal appear at particular risk for underweight. These results suggest that an adequate amount of body fat is necessary for optimal growth and bone health in patients with Thal, and that calcium intake is associated with optimal body composition. These preliminary findings support the need for more careful study of nutritional status and its relationship to overall health in patients with thalassemia.

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Changes in Bone Mineral Density Associated with Dietary-Induced Loss of Body Mass in Young Women

Clinical Science ◽

10.1042/cs0870343 ◽

1994 ◽

Vol 87 (3) ◽

pp. 343-348 ◽

Cited By ~ 58

Author(s):

S. J. Ramsdale ◽

E. J. Bassey

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Body Mass ◽

Bone Mineral ◽

Dietary Restriction ◽

Calcium Intake ◽

Dietary Assessment ◽

Premenopausal Women ◽

Mineral Density ◽

Total Body

1. Moderately overweight, premenopausal women were assessed for bone mineral density of the total body, lumbar spine and proximal femur before and after 6 months of modest dietary restriction (minimum 4800 kJ/day). The aim was to evaluate the effect of loss of body mass on bone mineral density. 2. Dietary assessment included two analyses of 3 day weighed food intakes, one before and the other after 4 months of dietary restriction. Energy and calcium intakes were significantly reduced by 27% and 5%, respectively. The change in calcium intake was negatively and significantly related to initial levels of calcium intake. 3. A significant mean loss of 3.4 ± 3.1 kg in body mass was achieved mainly in the first 3 months of the study; it was accompanied by significant losses at 6 months in bone mineral density in the total body of 0.7% and in the lumbar spine of 0.5%. There were no changes in the femur. 4. The change in bone mineral density in the total body was significantly related to the reduced absolute calcium intake, initial bone mineral density and loss of body mass. The change in bone mineral density in the spine was significantly related to the change in calcium intake. 5. These modest losses could be a threat in women with lower bone mineral density, and indicate the importance of maintaining a high intake of calcium during dietary restriction.

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Serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, and its relationship to bone health indices in Danish girls

British Journal Of Nutrition ◽

10.1017/s0007114507433050 ◽

2007 ◽

Vol 97 (4) ◽

pp. 661-666 ◽

Cited By ~ 36

Author(s):

Eibhlis O'Connor ◽

Christian Mølgaard ◽

Kim F. Michaelsen ◽

Jette Jakobsen ◽

Christel J. E. Lamberg-Allardt ◽

...

Keyword(s):

Lumbar Spine ◽

Bone Resorption ◽

Bone Turnover ◽

Vitamin K ◽

Bone Health ◽

Undercarboxylated Osteocalcin ◽

Pubertal Stage ◽

Cross Sectional ◽

Total Body ◽

Markers Of Bone Resorption

Recent cross-sectional data suggest that better vitamin K status in young girls (aged 3–16 years) is associated with decreased bone turnover, even though it is not associated with bone mineral content (BMC). The objective of the present study was to investigate the relationship between serum percentage of undercarboxylated osteocalcin (%ucOC), as an index of vitamin K status, and BMC and biochemical indices of bone turnover in peri-pubertal Danish girls. This peri-pubertal stage is a dynamic period of bone development, and as such, may represent an important window of opportunity for vitamin K status to modulate childhood bone health. Serum %ucOC and serum 25-hydroxyvitamin D (25 (OH) D) were measured at baseline in a study of 223 healthy girls aged 11–12 years. Urinary pyridinium crosslinks of collagen and serum total osteocalcin as markers of bone resorption and formation, respectively, as well as BMC (total body and lumbar spine) were also measured. Serum %ucOC (median 21·9 %) was not associated with markers of bone resorption or with total osteocalcin. Serum %ucOC was inversely correlated with serum 25 (OH) D (r− 0·143;P < 0·05). Serum %ucOC was negatively associated with BMC of the total body (β − 0·045;P < 0·001) and lumbar spine (β − 0·055;P < 0·05), after adjustment for potential confounders including vitamin D status. Better vitamin K status was associated with increased BMC, but not bone turnover, in healthy peri-pubertal Danish girls. There is a need for well-designed, randomized phylloquinone supplementation trials in children and adolescents to confirm epidemiological findings of an association between vitamin K status and bone health.

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Association between physical activity and bone in children with Prader-Willi syndrome

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2015-0233 ◽

2016 ◽

Vol 29 (7) ◽

Cited By ~ 2

Author(s):

Andrea T. Duran ◽

Kathleen S. Wilson ◽

Diobel M. Castner ◽

Jared M. Tucker ◽

Daniela A. Rubin

Keyword(s):

Physical Activity ◽

Bone Mineral ◽

Bone Health ◽

Mineral Content ◽

Moderate Intensity ◽

Prader Willi Syndrome ◽

Z Score ◽

Mineral Density ◽

Total Body ◽

Body Bone

AbstractThe aim of the study was to determine if physical activity (PA) is associated with bone health in children with Prader-Willi syndrome (PWS).Participants included 23 children with PWS (age: 11.0±2.0 years). PA, measured by accelerometry, was categorized into light, moderate, vigorous and moderate plus vigorous intensities. Hip, total body minus the head (body), bone mineral content (BMC), bone mineral density (BMD) and BMD z-score (BMDModerate PA and select covariates explained the most variance in hip BMC (84.0%), BMD (61.3%) and BMDPA of at least moderate intensity appears important for BMC and BMD in children with PWS.

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Ordinary Origins of Psychological Problems

10.1093/med/9780197607909.003.0008 ◽

2021 ◽

pp. 164-186

Author(s):

Benjamin B. Lahey

Keyword(s):

Genetic Variants ◽

Genetic Risk ◽

Molecular Genetic ◽

Psychological Problems ◽

Genetic Influences ◽

Polygenic Risk Score ◽

Nucleotide Polymorphisms ◽

Gene Environment ◽

Basic Biology ◽

Single Allele

This chapter summarizes the basic biology of inheritance, including chromosomes, genes, nucleotides, genotype, and gene expression. It uses these concepts and the logic of studies of the two kinds of twins—monozygotic and dizygotic—to define the concept of heritability as the proportion of differences on the dimension among people in the population that is attributable to genetic factors. The genetic variance in the phenotypes of psychological problems, such as depression, is never encoded in a single allele or genetic variant. Rather, every dimension of psychological problems is polygenic, meaning that many genetic variants have very small genetic influences on each dimension of psychological problems that must be combined to meaningfully measure the genetic component of risk at the molecular level. Often, single variations in individual nucleotides—the molecules arranged on DNA that serve as the letters of the genetic code—known as single nucleotide polymorphisms are summed to quantify the molecular genetic risk in a polygenic risk score. The nonspecific genetic influences at the top of the hierarchy of genetic influences result from some genetic variants being pleiotropic in the sense of directly or indirectly influencing essentially all dimensions of psychological problems. Identifying the specific genetic and environmental influences on dimensions of psychological problems at each level of the hierarchy is complicated because they operate together through the crucially important gene–environment correlations and interactions described in this chapter.

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Predictors of bone mineral density in a convenience sample of young Caucasian adults living in southern Ontario

Applied Physiology Nutrition and Metabolism ◽

10.1139/h2012-049 ◽

2012 ◽

Vol 37 (4) ◽

pp. 706-714 ◽

Cited By ~ 5

Author(s):

Laura E. Chouinard ◽

Janis Randall Simpson ◽

Andrea C. Buchholz

Keyword(s):

Physical Activity ◽

Bone Mineral Density ◽

Body Mass ◽

Bone Mineral ◽

Bone Health ◽

Calcium Intake ◽

Health Concern ◽

Mineral Density ◽

Southern Ontario ◽

Men And Women

Osteoporosis is a major public health concern in Canada and worldwide. Although much is known about bone health in older adults, little is known about bone health in young, healthy Canadian men and women. The objectives of this research were to describe bone mineral density (BMD) of young, healthy adults living in southern Ontario, Canada, and to identify predictors of BMD in this population. Two-hundred and fifty-eight Caucasian men and women aged 18–33 years completed health and physical activity questionnaires along with a calcium and vitamin D specific food frequency questionnaire. Height and mass were measured. BMD of the total hip, femoral neck, spine, and total body was measured using dual energy X-ray absorptiometry. Among men, body mass, weight-bearing physical activity, and calcium intake were significant predictors of BMD. Among women, body mass, calcium intake, and family history of osteoporosis significantly predicted log BMD. The predictors of BMD in young Canadian men and women identified in this study may inform the development of longitudinal studies designed to examine the influence of lifestyle factors on BMD in young adults.

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Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations

PLoS ONE ◽

10.1371/journal.pone.0258748 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258748

Author(s):

Dmitrii Borisevich ◽

Theresia M. Schnurr ◽

Line Engelbrechtsen ◽

Alexander Rakitko ◽

Lars Ängquist ◽

...

Keyword(s):

Physical Activity ◽

Body Mass Index ◽

Environmental Factors ◽

Body Mass ◽

Risk Score ◽

Polygenic Risk Score ◽

Environment Interaction ◽

Linear Interaction ◽

Polygenic Risk ◽

Non Linear

Body mass index (BMI) is a highly heritable polygenic trait. It is also affected by various environmental and behavioral risk factors. We used a BMI polygenic risk score (PRS) to study the interplay between the genetic and environmental factors defining BMI. First, we generated a BMI PRS that explained more variance than a BMI genetic risk score (GRS), which was using only genome-wide significant BMI-associated variants (R2 = 13.1% compared to 6.1%). Second, we analyzed interactions between BMI PRS and seven environmental factors. We found a significant interaction between physical activity and BMI PRS, even when the well-known effect of the FTO region was excluded from the PRS, using a small dataset of 6,179 samples. Third, we stratified the study population into two risk groups using BMI PRS. The top 22% of the studied populations were included in a high PRS risk group. Engagement in self-reported physical activity was associated with a 1.66 kg/m2 decrease in BMI in this group, compared to a 0.84 kg/m2 decrease in BMI in the rest of the population. Our results (i) confirm that genetic background strongly affects adult BMI in the general population, (ii) show a non-linear interaction between BMI genetics and physical activity, and (iii) provide a standardized framework for future gene-environment interaction analyses.

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