We have previously shown that multiple genetic loci identified by genome-wide association studies (GWAS) increase the susceptibility to obesity in a cumulative manner. It is, however, not known ...whether and to what extent this genetic susceptibility may be attenuated by a physically active lifestyle. We aimed to assess the influence of a physically active lifestyle on the genetic predisposition to obesity in a large population-based study.
We genotyped 12 SNPs in obesity-susceptibility loci in a population-based sample of 20,430 individuals (aged 39-79 y) from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort with an average follow-up period of 3.6 y. A genetic predisposition score was calculated for each individual by adding the body mass index (BMI)-increasing alleles across the 12 SNPs. Physical activity was assessed using a self-administered questionnaire. Linear and logistic regression models were used to examine main effects of the genetic predisposition score and its interaction with physical activity on BMI/obesity risk and BMI change over time, assuming an additive effect for each additional BMI-increasing allele carried. Each additional BMI-increasing allele was associated with 0.154 (standard error SE 0.012) kg/m(2) (p = 6.73 x 10(-37)) increase in BMI (equivalent to 445 g in body weight for a person 1.70 m tall). This association was significantly (p(interaction) = 0.005) more pronounced in inactive people (0.205 SE 0.024 kg/m(2) p = 3.62 x 10(-18); 592 g in weight) than in active people (0.131 SE 0.014 kg/m(2) p = 7.97 x 10(-21); 379 g in weight). Similarly, each additional BMI-increasing allele increased the risk of obesity 1.116-fold (95% confidence interval CI 1.093-1.139, p = 3.37 x 10(-26)) in the whole population, but significantly (p(interaction) = 0.015) more in inactive individuals (odds ratio OR = 1.158 95% CI 1.118-1.199; p = 1.93 x 10(-16)) than in active individuals (OR = 1.095 (95% CI 1.068-1.123; p = 1.15 x 10(-12)). Consistent with the cross-sectional observations, physical activity modified the association between the genetic predisposition score and change in BMI during follow-up (p(interaction) = 0.028).
Our study shows that living a physically active lifestyle is associated with a 40% reduction in the genetic predisposition to common obesity, as estimated by the number of risk alleles carried for any of the 12 recently GWAS-identified loci. Please see later in the article for the Editors' Summary.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flavonoids are a group of phenolic secondary plant metabolites that are ubiquitous in plant-based diets. Data from anthropological, observational and intervention studies have shown that many ...flavonoids are bioactive. For this reason, there is an increasing interest in investigating the potential health effects of these compounds. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations.
The objective of this study is to determine the habitual intake and main sources of anthocyanidins, flavanols, flavanones, flavones, flavonols, proanthocyanidins, theaflavins and thearubigins in the European Union.
We use food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database to estimate intake of flavonoids.
Mean (±SEM) intake of total flavonoids in Europe was 428±49 mg/d, of which 136±14 mg/d were monomeric compounds. Gallated flavan-3-ols (53±12 mg/d) were the main contributor. The lowest flavonoid intake was observed in Mediterranean countries (monomeric compounds: 95±11 mg/d). The distribution of intake was skewed in many countries, especially in Germany (monomeric flavonoids; mean intake: 181 mg/d; median intake: 3 mg/d).
The habitual intake of flavonoids in Europe is below the amounts found to have a significant health effect.
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OBJECTIVE: The association between quantity of fruit and vegetable (F&V) intake and risk of type 2 diabetes (T2D) is not clear, and the relationship with variety of intake is unknown. The current ...study examined the association of both quantity and variety of F&V intake and risk of T2D. RESEARCH DESIGN AND METHODS: We examined the 11-year incidence of T2D in relation to quantity and variety of fruit, vegetables, and combined F&V intake in a case-cohort study of 3,704 participants (n = 653 diabetes cases) nested within the European Prospective Investigation into Cancer and Nutrition-Norfolk study, who completed 7-day prospective food diaries. Variety of intake was derived from the total number of different items consumed in a 1-week period. Multivariable, Prentice-weighted Cox regression was used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A greater quantity of combined F&V intake was associated with 21% lower hazard of T2D (HR 0.79 95% CI 0.62–1.00) comparing extreme tertiles, in adjusted analyses including variety. Separately, quantity of vegetable intake (0.76 0.60–0.97), but not fruit, was inversely associated with T2D in adjusted analysis. Greater variety in fruit (0.70 0.53–0.91), vegetable (0.77 0.61–0.98), and combined F&V (0.61 0.48–0.78) intake was associated with a lower hazard of T2D, independent of known confounders and quantity of intake comparing extreme tertiles. CONCLUSIONS: These findings suggest that a diet characterized by a greater quantity of vegetables and a greater variety of both F&V intake is associated with a reduced risk of T2D.
To study the utility of body fat percentage in predicting health outcomes when other obesity indices are considered.
We conducted a prospective cohort study to evaluate the independent utility of ...body fat percentage and other obesity indices in predicting mortality and cardiovascular disease (CVD).
We prospectively followed 15 062 European Prospective Investigation into Cancer (EPIC)-Norfolk participants who attended a health examination during 1997–2000 for all-cause mortality and incidence of CVD up to end of December 2011 and end of March 2009, respectively. During the follow-up, 2420 died and 4665 had incident CVD. After exclusion of prior stroke, myocardial infarction and cancer and adjusting for potential confounders, body mass index (BMI) and waist-to- hip ratio (WHR), the HR of mortality for men were 0.86 (0.68 to 1.09), 0.81 (0.61 to 1.07) and 0.76 (0.55 to 1.05) and for women were 0.91 (0.70 to 1.17), 0.75 (0.55 to 1.02) and 0.87 (0.61 to 1.23) for second, third and fourth quartile compared with the first (bottom) quartile of body fat percentage. The respective HRs for incident CVD were 0.99 (0.83 to 1.19), 0.85 (0.69 to 1.04) and 0.81 (0.64 to 1.03) for men and 0.98 (0.82 to 1.17), 0.89 (0.73 to 1.10) and 1.02 (0.81 to 1.29) for women. In contrast, higher BMI and WHR were associated with an increased risk of both outcomes and WHR appeared to have the best predictive value among three indices.
Once BMI and WHR are taken into account, fat percentage does not add to prediction of mortality or CVD in middle-aged and older-aged adults.
Research on Mediterranean diet (MD) adherence and musculoskeletal health is limited. The current study determined if adherence to the alternative MD score (aMED) and MD score (MDS), quantified from ...7-d food diaries, was associated with fracture incidence, bone density (calcaneal broadband ultrasound attenuation (BUA)) and fat free mass (expressed over BMI (FFM
) using bioelectrical impedance) in 25,450 men and women recruited to the European Prospective Investigation into Cancer study in Norfolk, UK. During 17.4 years of follow up (443,178 total person years) 2195 incident fractures occurred. Higher aMED adherence was associated with 23% reduced total (Q5-Q1 HR 0.77; 95% CI 0.67, 0.88;
-trend < 0.01) and 21% reduced hip (Q5-Q1 HR 0.79; 95% CI 0.65, 0.96;
-trend = 0.01) fracture incidence, and significantly higher BUA (Q5-Q1 1.0 dB/MHz 95% CI 0.2, 1.9;
-trend < 0.01) and FFM
(Q5-Q1 0.05 kg/(kg/m
) 95% CI 0.04, 0.06;
-trend < 0.01), comparing extreme adherence quintiles. Higher MDS was also associated with reduced total fractures (Q5-Q1 HR 0.83; 95% CI 0.71, 0.96;
-trend = 0.03) and significantly higher BUA (Q5-Q1 1.4 dB/MHz 95% CI 0.5, 2.3;
-trend < 0.01) and FFM
(Q5-Q1 0.03 kg/(kg/m
) 95% CI 0.01, 0.04;
-trend < 0.01). This evidence supports the need to develop interventions to enhance MD adherence, particularly in women, where evidence for associations was stronger.
The American Heart Association has prioritised seven cardiovascular health metrics to reduce the cardiovascular burden, including: body mass index, healthy diet, physical activity, smoking status, ...blood pressure, glycated haemoglobin A1c and total cholesterol. The aim of the current study was to assess the association between the American Heart Association-defined health metrics and the risk of cardiovascular events in the EPIC-Norfolk prospective study.
Prospective cohort study.
An overall cardiovascular health score was calculated based on the number of health metrics including ideal, intermediate or poor. Cox proportional hazards models were used to describe the association of the seven metrics separately and the overall health score with risk of coronary heart disease, stroke and cardiovascular disease. A total of 10,043 participants was included in the analysis (follow-up 1993-2008). For all individual health metrics a more ideal status was associated with a lower risk of cardiovascular events.
As for the overall cardiovascular health score, those in the highest (i.e. healthiest) category (score 12-14) had an adjusted hazard ratio for coronary heart disease of 0.07 (95% confidence interval (CI) 0.02-0.29, P < 0.001), for stroke of 0.16 (95% CI 0.02-1.37, P = 0.09) and for cardiovascular disease of 0.07 (95% CI 0.02-0.23, P < 0.001), compared to people in the lowest (i.e. unhealthiest) category (score 0-2). The overall cardiovascular health score was strongly and inversely associated with risk of coronary heart disease, stroke and cardiovascular disease. Our data suggest that even small improvements in modifiable risk factors may lead to substantial reductions in the risks of cardiovascular events.
Chronic obstructive pulmonary disease is known to be associated with systemic inflammation. We examined the longitudinal association of C-reactive protein (CRP) and lung function in a cohort of ...18,110 men and women from the European Prospective Investigation Into Cancer in Norfolk who were 40-79 years of age at baseline (recruited in 1993-1997) and followed-up through 2011. We assessed lung function by measuring forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) at baseline, 4 years, and 13 years. Serum CRP levels were measured using a high-sensitivity assay at baseline and the 13-year follow up. Cross-sectional and longitudinal associations of loge-CRP and lung function were examined using multivariable linear mixed models. In the cross-sectional analysis, 1-standard-deviation increase in baseline loge-CRP (about 3-fold higher CRP on the original milligrams per liter scale) was associated with a -86.3 mL (95% confidence interval: -93.9, -78.6) reduction in FEV1. In longitudinal analysis, a 1-standard-deviation increase in loge-CRP over 13 years was also associated with a -64.0 mL (95% confidence interval: -72.1, -55.8) decline in FEV1 over the same period. The associations were similar for FVC and persisted among lifetime never-smokers. Baseline CRP levels were not predictive of the rate of change in FEV1 or FVC over time. In the present study, we found longitudinal observational evidence that suggested that increases in systemic inflammation are associated with declines in lung function.
To examine the association of physical activity (PA) with glaucoma and related traits, to assess whether genetic predisposition to glaucoma modified these associations, and to probe causal ...relationships using Mendelian randomization (MR).
Cross-sectional observational and gene–environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia.
UK Biobank participants with data on self-reported or accelerometer-derived PA and intraocular pressure (IOP; n = 94 206 and n = 27 777, respectively), macular inner retinal OCT measurements (n = 36 274 and n = 9991, respectively), and glaucoma status (n = 86 803 and n = 23 556, respectively).
We evaluated multivariable-adjusted associations of self-reported (International Physical Activity Questionnaire) and accelerometer-derived PA with IOP and macular inner retinal OCT parameters using linear regression and with glaucoma status using logistic regression. For all outcomes, we examined gene–PA interactions using a polygenic risk score (PRS) that combined the effects of 2673 genetic variants associated with glaucoma.
Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell–inner plexiform layer (mGCIPL) thickness, and glaucoma status.
In multivariable-adjusted regression models, we found no association of PA level or time spent in PA with glaucoma status. Higher overall levels and greater time spent in higher levels of both self-reported and accelerometer-derived PA were associated positively with thicker mGCIPL (P < 0.001 for trend for each). Compared with the lowest quartile of PA, participants in the highest quartiles of accelerometer-derived moderate- and vigorous-intensity PA showed a thicker mGCIPL by +0.57 μm (P < 0.001) and +0.42 μm (P = 0.005). No association was found with mRNFL thickness. High overall level of self-reported PA was associated with a modestly higher IOP of +0.08 mmHg (P = 0.01), but this was not replicated in the accelerometry data. No associations were modified by a glaucoma PRS, and MR analyses did not support a causal relationship between PA and any glaucoma-related outcome.
Higher overall PA level and greater time spent in moderate and vigorous PA were not associated with glaucoma status but were associated with thicker mGCIPL. Associations with IOP were modest and inconsistent. Despite the well-documented acute reduction in IOP after PA, we found no evidence that high levels of habitual PA are associated with glaucoma status or IOP in the general population.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Background: Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. Several NOCs are potential human carcinogens, including N-nitrosodimethylamine (NDMA), but evidence from ...population studies is inconsistent.
Objective: We examined the relation between dietary NOCs (NDMA), the endogenous NOC index, and dietary nitrite and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk, United Kingdom, study.
Design: This was a prospective study of 23,363 men and women, aged 40–79 y, who were recruited in 1993–1997 and followed up to 2008. The baseline diet was assessed with food-frequency questionnaires.
Results: There were 3268 incident cancers after a mean follow-up of 11.4 y. Dietary NDMA intake was significantly associated with increased cancer risk in men and women hazard ratio (HR): 1.14; 95% CI: 1.03, 1.27; P for trend = 0.03 and in men (HR: 1.24; 95% CI: 1.07, 1.44; P for trend = 0.005) when the highest quartile was compared with the lowest quartile in age- and sex-adjusted analyses but not in multivariate analyses (HR: 1.10; 95% CI: 0.97, 1.24; HR for men: 1.18; 95% CI: 1.00, 1.40; P for trend ≥ 0.05). When continuously analyzed, NDMA was associated with increased risk of gastrointestinal cancers (HR: 1.13; 95% CI: 1.00, 1.28), specifically of rectal cancer (HR: 1.46; 95% CI: 1.16, 1.84) per 1-SD increase after adjustment for age, sex, body mass index, cigarette smoking status, alcohol intake, energy intake, physical activity, education, and menopausal status (in women). The endogenous NOC index and dietary nitrite were not significantly associated with cancer risk. There was a significant interaction between plasma vitamin C concentrations and dietary NDMA intake on cancer incidence (P for interaction < 0.00001).
Conclusions: Dietary NOC (NDMA) was associated with a higher gastrointestinal cancer incidence, specifically of rectal cancer. Plasma vitamin C may modify the relation between NDMA exposure and cancer risk.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND: Large-scale genome-wide association studies have identified 12 genetic loci that are robustly associated with body mass index (BMI). OBJECTIVES: We examined associations and compared ...effect sizes of these newly identified obesity susceptibility loci with various anthropometric traits and assessed their cumulative effects and predictive value for obesity risk. DESIGN: We genotyped 12 single nucleotide polymorphisms (SNPs) from each locus in 20,431 individuals (age: 39-79 y) from the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. General linear model and logistic regression were used to examine associations, and the area under the receiver operating characteristic curve (AUC) was used to assess the predictive value of these variants for obesity risk. RESULTS: Effect sizes of the risk alleles ranged between 0.058 and 0.329 for BMI (in kg/m²), between 0.094 and 0.866 kg for weight, and between 0.085 and 0.819 cm for waist circumference, with rs1121980 (FTO locus) showing the largest effect. Risk alleles of rs7132908 (FAIM2 locus) and rs17782313 (MC4R locus) were also associated with taller height. On average, each additional risk allele was associated with increases of 0.149 in BMI (P = 1.54 x 10⁻²²), 0.444 kg in body weight (P = 9.88 x 10⁻²²), and 0.357 cm in waist circumference (P = 1.10 x 10⁻¹⁸) and 10.8% (P = 9.83 x 10⁻¹⁶) and 5.5% (P = 3.38 x 10⁻¹⁰) increased risks of obesity and overweight, respectively. All SNPs combined explained 0.9% of BMI variation, with an AUC of 0.574 (95% CI: 0.559, 0.590) for prediction of obesity. CONCLUSIONS: Common variants for BMI have small effects on obesity measures and show different association patterns with anthropometric traits, with the largest effect shown for the FTO locus. These variants have cumulative effects, yet their predictive value for obesity risk is limited.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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