Ideal body image for the opposite sex and its association with body mass index.

This research studied the preferences reported by women and men about their Ideal Body Image for the Opposite Sex (IBIOS), and its association with body mass index (BMI). It also analysed the preferences of each sex for a woman's ideal body image (W-IBI) and a man's ideal body image (M-IBI). A total of 450 participants aged 18-70 years with different weights were studied. Their IBIOS was assessed using standard figural stimuli. The sample was divided in four groups by sex and age (<45 years; ≥45 years). Sex and age differences in IBIOS, as well as sex differences in the preferences for a woman's ideal body image (W-IBI) and a man's ideal body image (M-IBI), were tested using a non-parametric Mann-Whitney U test. The association between IBIOS and BMI was analysed using Spearman's correlation. In all groups, the most chosen silhouette as IBIOS was number 4. In the under-45 years group, women chose bigger silhouettes for the opposite sex than men did (p<0.05). In this age group women chose as ideal smaller silhouettes for the female body than men did (p<0.01). In addition, women and men in the younger age group and with normal weight chose smaller silhouettes, while those who were overweight or obese selected larger silhouettes (p<0.001). Age was found to be a relevant factor in IBIOS preferences, and in the association between IBIOS and nutritional status as measured by BMI, which was only observed to be significant in the younger age group.

European Roma groups show complex West Eurasian admixture footprints and a common South Asian genetic origin.

The Roma population is the largest transnational ethnic minority in Europe, characterized by a linguistic, cultural and historical heterogeneity. Comparative linguistics and genetic studies have placed the origin of European Roma in the Northwest of India. After their migration across Persia, they entered into the Balkan Peninsula, from where they spread into Europe, arriving in the Iberian Peninsula in the 15th century. Their particular demographic history has genetic implications linked to rare and common diseases. However, the South Asian source of the proto-Roma remains still untargeted and the West Eurasian Roma component has not been yet deeply characterized. Here, in order to describe both the South Asian and West Eurasian ancestries, we analyze previously published genome-wide data of 152 European Roma and 34 new Iberian Roma samples at a fine-scale and haplotype-based level, with special focus on the Iberian Roma genetic substructure. Our results suggest that the putative origin of the proto-Roma involves a Punjabi group with low levels of West Eurasian ancestry. In addition, we have identified a complex West Eurasian component (around 65%) in the Roma, as a result of the admixture events occurred with non-proto-Roma populations between 1270-1580. Particularly, we have detected the Balkan genetic footprint in all European Roma, and the Baltic and Iberian components in the Northern and Western Roma groups, respectively. Finally, our results show genetic substructure within the Iberian Roma, with different levels of West Eurasian admixture, as a result of the complex historical events occurred in the Peninsula.

Body image in relation to nutritional status in adults from the Basque Country, Spain.

The aim of this research was to analyse variation in body image perception and satisfaction by age, sex and nutritional status in an adult sample from the Basque Country, Spain. A case-control study was performed for 227 women and 178 men aged 18-70 years. Stunkard's silhouettes were used to evaluate Current Body Image (CBI) and Ideal Body Image (IBI), as well as dissatisfaction and inconsistency scores. Nutritional status was assessed following the WHO criteria for BMI in an adult population. The sample was divided into four groups based on sex and age (early adulthood <45 years, and middle/older adulthood ≥45 years). The Mann-Whitney U test was employed to evaluate sex and age differences, and the Gamma coefficient to assess the association between body image variables and nutritional status. Significant age differences in CBI (p<0.05) and sex differences in IBI (p<0.001) were detected. Both variables showed a positive association with BMI (p<0.01), which indicates that BMI is a biological characteristic related to body image satisfaction and influences participants' perception of themselves. Dissatisfaction scores showed that both sex and age differences (p<0.05) were negatively associated with BMI (p<0.001). Only participants ≥45 years presented sex differences in inconsistency scores (p<0.05); this variable was associated with BMI in women (p<0.01). Preferences in body image showed sexual dimorphism, with women preferring thinner bodies than men - a pattern observed in many Western populations - linked in part to sociocultural pressures. Women were more dissatisfied with their bodies than men; a higher dissatisfaction was observed in older relative to younger participants. The results confirm the association between nutritional status and body size perception and satisfaction, but also the relationship between nutritional status and the reliability with which women can classify themselves; in men, this relationship was not as clear.

The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden: the GLACIER Study.

BACKGROUND: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential. METHODS: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used. RESULTS: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score. CONCLUSIONS: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. However, our results suggest that multiple haplotypes may harbour functional variants in a region, rather than a single causal variant.

Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

AIMS/HYPOTHESIS: Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. METHODS: We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. RESULTS: No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. CONCLUSIONS/INTERPRETATION: Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.

Tau haplotypes support the Asian ancestry of the Roma population settled in the Basque Country.

We examined tau haplotype frequencies in two different ethnical groups from the Basque Country (BC): Roma people and residents of European ancestry (general population). In addition, we analyzed the spatial distribution of tau haplotypes in Eurasian populations to explore the genetic affinities of the Romani groups living in Europe in a broader scope. The 17q21.31 genomic region was characterized through the genotyping of two diagnostic single nucleotide polymorphisms, SNPs (rs10514879 and rs199451), which allow the identification of H1 and H2 haplotypes. A significant heterozygous deficit was detected in the Romani for rs10514879. The H2 haplotype frequency proved to be more than twice in the BC general population (0.283) than in the Roma people (0.127). In contrast, H2 frequency proved to be very similar between Basque and Hungarian Romani, and similar to the H2 frequencies found in northwestern India and Pakistan as well. Several statistical analyses unveiled genetic structuring for the MAPT diversity, mirrored in a significant association between geography and genetic distances, with an upward trend of H2 haplotype frequencies from Asia to Europe. Yet, Roma samples did not fit into this general spatial patterning because of their discrepancy between geographical position and H2 frequency. Despite the long spatial coexistence in the Basque region between the residents of European ancestry and the Roma, the latter have preserved their Asian genetic ancestry. Bearing in mind the lack of geographical barriers between both ethnical groups, these findings support the notion that sociocultural mores might promote assortative matings in human populations.

Lifestyle and precision diabetes medicine: will genomics help optimise the prediction, prevention and treatment of type 2 diabetes through lifestyle therapy?

Precision diabetes medicine, the optimisation of therapy using patient-level biomarker data, has stimulated enormous interest throughout society as it provides hope of more effective, less costly and safer ways of preventing, treating, and perhaps even curing the disease. While precision diabetes medicine is often framed in the context of pharmacotherapy, using biomarkers to personalise lifestyle recommendations, intended to lower type 2 diabetes risk or to slow progression, is also conceivable. There are at least four ways in which this might work: (1) by helping to predict a person's susceptibility to adverse lifestyle exposures; (2) by facilitating the stratification of type 2 diabetes into subclasses, some of which may be prevented or treated optimally with specific lifestyle interventions; (3) by aiding the discovery of prognostic biomarkers that help guide timing and intensity of lifestyle interventions; (4) by predicting treatment response. In this review we overview the rationale for precision diabetes medicine, specifically as it relates to lifestyle; we also scrutinise existing evidence, discuss the barriers germane to research in this field and consider how this work is likely to proceed.

The heritable basis of gene-environment interactions in cardiometabolic traits.

AIMS/HYPOTHESIS: Little is known about the heritable basis of gene-environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype-environment interactions. METHODS: Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software. RESULTS: All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h 2) ranging from 24% to 47%. Genotype-environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype-age interactions for weight and systolic BP, genotype-sex interactions for BMI and triacylglycerols and genotype-alcohol intake interactions for weight remained significant after multiple test correction. CONCLUSIONS/INTERPRETATION: Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease.

Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study.

AIMS/HYPOTHESIS: We compared the ability of genetic (established type 2 diabetes, fasting glucose, 2 h glucose and obesity variants) and modifiable lifestyle (diet, physical activity, smoking, alcohol and education) risk factors to predict incident type 2 diabetes and obesity in a population-based prospective cohort of 3,444 Swedish adults studied sequentially at baseline and 10 years later. METHODS: Multivariable logistic regression analyses were used to assess the predictive ability of genetic and lifestyle risk factors on incident obesity and type 2 diabetes by calculating the AUC. RESULTS: The predictive accuracy of lifestyle risk factors was similar to that yielded by genetic information for incident type 2 diabetes (AUC 75% and 74%, respectively) and obesity (AUC 68% and 73%, respectively) in models adjusted for age, age(2) and sex. The addition of genetic information to the lifestyle model significantly improved the prediction of type 2 diabetes (AUC 80%; p = 0.0003) and obesity (AUC 79%; p < 0.0001) and resulted in a net reclassification improvement of 58% for type 2 diabetes and 64% for obesity. CONCLUSIONS/INTERPRETATION: These findings illustrate that lifestyle and genetic information separately provide a similarly high degree of long-range predictive accuracy for obesity and type 2 diabetes.

Common variants in BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1 show association with obesity-related variables in Spanish Roma population.

OBJECTIVES: The objective of this study is to investigate the association between previously GWAS identified genetic variants predisposing to obesity in Europeans and obesity-related phenotypes in Roma population. METHODS: A total of 24 representative single nucleotide polymorphisms (SNPs) were genotyped in 372 individuals belonging to 50 extended families of Roma population. SNPs were tested for association with seven quantitative obesity-related phenotypes in the PLINK program. RESULTS: Risk variants in NEGR1, FAIM2, FTO, and SH2B1 genes were associated with increased adiposity accumulation in Roma population with effect sizes between 0.21 and 0.34 Z-scores for each copy of the BMI increasing allele. Additionally, variants in BDNF and MC4R were significantly associated with adiposity distribution but not with overall fatness. No significant association was detected between obesity-related phenotypes and variants in the first intron of the FTO gene (e.g., rs9939609). CONCLUSIONS: The results of this study suggest that SNPs in or near six genes (BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1) are significantly associated with body fat accumulation and distribution in Roma people. However, the association observed among variants in the first intron of FTO and obesity in European derived populations is not evident in the analyzed Roma sample.

Obesity and body size perceptions in a Spanish Roma population.

BACKGROUND: Roma people are particularly vulnerable to developing overweight and obesity. Self-perception of body image may influence the prevalence of obesity in this ethnic minority. AIM: The objectives of this study are to estimate the prevalence of obesity, to analyse body size perceptions and preferences and to assess the relationship between body size perceptions and obesity in the Roma population. SUBJECTS AND METHODS: The analyses were carried out on 372 men, women and children from the Roma population residing in the Greater Bilbao region (Basque Country, Spain). In adults, a standard figural scale was used to analyse body size perceptions and preferences in this ethnic minority. RESULTS: Overall 51.7% of adult and 24.4% of minor Roma individuals were obese. Both Roma men and women had inaccurate self-perceptions of their body size. Significant differences on body size perceptions were detected based on age, sex, nutritional status and socioeconomic characteristics. CONCLUSION: This Roma population presents one of the highest rates of obesity worldwide. Although a certain awareness of the correct weight status was appreciated, the inability of Roma individuals to see themselves as overweight or obese may be a significant factor on the high prevalence of obesity in this population.

A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes.

Obesity and type 2 diabetes are causally related, yet there is considerable heterogeneity in the consequences of both conditions and the mechanisms of action are poorly defined. Here we show a genetic-driven approach defining two obesity profiles that convey highly concordant and discordant diabetogenic effects. We annotate and then compare association signals for these profiles across clinical and molecular phenotypic layers. Key differences are identified in a wide range of traits, including cardiovascular mortality, fat distribution, liver metabolism, blood pressure, specific lipid fractions and blood levels of proteins involved in extracellular matrix remodelling. We find marginal differences in abundance of Bacteroidetes and Firmicutes bacteria in the gut. Instrumental analyses reveal prominent causal roles for waist-to-hip ratio, blood pressure and cholesterol content of high-density lipoprotein particles in the development of diabetes in obesity. We prioritize 17 genes from the discordant signature that convey protection against type 2 diabetes in obesity, which may represent logical targets for precision medicine approaches.

Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Heritability and genetic correlations of obesity-related phenotypes among Roma people.

BACKGROUND: The Roma people are particularly vulnerable to developing obesity and related diseases, due to their social and ethnic backgrounds. However, little is known about the genetic and/or environmental factors affecting the variability of obesity-related traits among the Roma population. AIM: The aim of the present study was to estimate heritabilities and common genetic and environmental influences of obesity-related phenotypes in a sample of Roma people living in the Greater Bilbao region (Basque Country; Spain). SUBJECTS AND METHODS: Three hundred and seventy-two individuals from 50 large, extended and highly consanguineous pedigrees were phenotyped for anthropometric traits related to obesity. Heritability estimates were assessed for all quantitative traits and bivariate analyses were conducted to assess the phenotypic, genetic and environmental correlations among these traits. RESULTS: Significant heritable components (p<0.01) ranging from 0.25-0.68 exist for the studied phenotypes. Heritability for WHR (h(2) =0.60) considerably surpasses the usual heritability estimates on family-based studies ( <0.30). Measures of overall fatness (BMI, CF and SF) show stronger correlations with each other than body fat distribution traits (WHR, CI and TER). CONCLUSIONS: The study concluded that the Greater Bilbao Roma population is genetically predisposed to abdominal fat distribution. Variation in body mass is highly associated with variation in adiposity. However, overall fatness and adiposity distribution does not seem to share major common genetic factors, although common environmental factors operate between them.

Predicting Sensitivity to Adverse Lifestyle Risk Factors for Cardiometabolic Morbidity and Mortality.

People appear to vary in their susceptibility to lifestyle risk factors for cardiometabolic disease; determining a priori who is most sensitive may help optimize the timing, design, and delivery of preventative interventions. We aimed to ascertain a person's degree of resilience or sensitivity to adverse lifestyle exposures and determine whether these classifications help predict cardiometabolic disease later in life; we pooled data from two population-based Swedish prospective cohort studies (n = 53,507), and we contrasted an individual's cardiometabolic biomarker profile with the profile predicted for them given their lifestyle exposure characteristics using a quantile random forest approach. People who were classed as 'sensitive' to hypertension- and dyslipidemia-related lifestyle exposures were at higher risk of developing cardiovascular disease (CVD, hazards ratio 1.6 (95% CI: 1.3, 1.91)), compared with the general population. No differences were observed for type 2 diabetes (T2D) risk. Here, we report a novel approach to identify individuals who are especially sensitive to adverse lifestyle exposures and who are at higher risk of subsequent cardiovascular events. Early preventive interventions may be needed in this subgroup.

Exposome-wide ranking of modifiable risk factors for cardiometabolic disease traits.

The present study assessed the temporal associations of ~ 300 lifestyle exposures with nine cardiometabolic traits  to identify exposures/exposure groups that might inform lifestyle interventions for the reduction of cardiometabolic disease risk. The analyses were undertaken in a longitudinal sample comprising > 31,000 adults living in northern Sweden. Linear mixed models were used to assess the average associations of lifestyle exposures and linear regression models were used to test associations with 10-year change in the cardiometabolic traits. 'Physical activity' and 'General Health' were the exposure categories containing the highest number of 'tentative signals' in analyses assessing the average association of lifestyle variables, while 'Tobacco use' was the top category for the 10-year change association analyses. Eleven modifiable variables showed a consistent average association among the majority of cardiometabolic traits. These variables belonged to the domains: (i) Smoking, (ii) Beverage (filtered coffee), (iii) physical activity, (iv) alcohol intake, and (v) specific variables related to Nordic lifestyle (hunting/fishing during leisure time and boiled coffee consumption). We used an agnostic, data-driven approach to assess a wide range of established and novel risk factors for cardiometabolic disease. Our findings highlight key variables, along with their respective effect estimates, that might be prioritised for subsequent prediction models and lifestyle interventions.

Quantitative genetics of human morphology and obesity-related phenotypes in nuclear families from the Greater Bilbao (Spain): comparison with other populations.

BACKGROUND: It is well established that variation of soft-tissue traits is less influenced by the genetic component than skeletal traits. However, it is still unclear whether heritabilities (h(2)) of obesity-related phenotypes present a common pattern across populations. AIM: To estimate familial resemblance and heritability of body size, shape and composition phenotypes and to compare these results with those from other populations. SUBJECTS AND METHODS: The subject group consisted of 533 nuclear families living in Greater Bilbao and included 1702 individuals aged 2-61 years. Familial correlations and h(2) were estimated for 29 anthropometric phenotypes (19 simple measures, three derived factors, four obesity indices and the three Heath-Carter somatotype components) using MAN and SOLAR programmes. RESULTS: All phenotypes were influenced by additive genetic factors with narrow sense heritabilities ranging from 0.28-0.69. In general, skeletal traits exhibited the highest h(2), whereas phenotypes defining the amount of adipose tissue, particularly central fat, were less determined by genetic factors. CONCLUSIONS: Familial correlations and heritability estimates of body morphology and composition from the Greater Bilbao sample were within the range observed in other studies. The lower heritability detected for central fat has also been found in some other populations, but further investigations in different populations using the same anthropometric traits and estimation methods are needed in order to obtain more robust conclusions.

Genetic contribution to variation in body configuration in Belgian nuclear families: a closer look at body lengths and circumferences.

The purpose of the current study was to evaluate the contribution of genetic factors on body configuration related phenotypes. The sample consisted of 119 Belgian nuclear families including 231 males and 229 females. Factor analysis with varimax rotation was carried out to analyse 13 length and circumference measures and the resulting two synthetic traits (LF and CF; linear and circumference factors, respectively) were used as summary variables. Univariate quantitative genetic analysis indicated that variation in anthropometric as well as in synthetic traits was significantly dependent on additive genetic effects, with heritabilities ranging from 0.55 to 0.88. Narrow sense heritability estimates were higher for measurements principally characterizing skeletal mass than in variables that also involve soft-tissues. Sex, age and their interactions explained 11-67% of the total phenotypic variance. This report also examined the covariations between pairs of anthropometric and synthetic traits (length measurements and LF vs. height; circumference measures and CF vs. weight and BMI; LF vs. CF). Significant genetic correlations among all the studied traits (except for middle finger length vs. height) confirmed the influence of pleiotropy on genetic determination of these phenotypes. Bivariate analysis showed that pleiotropic effects had a great influence in determining body traits variation within body length measurements, as well as between body circumferences and weight or BMI. In relation to the two synthetic traits, even the variation of body lengths and circumferences was highly determined by genetic factors, shared genetic influences were unlikely to explain much of the observed variation between LF and CF. The results of the present study allow us to conclude that in this population body configuration related traits are subject to a strong genetic control and that shared genes also contribute to this genetic structure.

Association of Established Blood Pressure Loci With 10-Year Change in Blood Pressure and Their Ability to Predict Incident Hypertension.

Background Genome-wide association studies have identified >1000 genetic variants cross-sectionally associated with blood pressure variation and prevalent hypertension. These discoveries might aid the early identification of subpopulations at risk of developing hypertension or provide targets for drug development, amongst other applications. The aim of the present study was to analyze the association of blood pressure-associated variants with long-term changes (10 years) in blood pressure and also to assess their ability to predict hypertension incidence compared with traditional risk variables in a Swedish population. Methods and Results We constructed 6 genetic risk scores (GRSs) by summing the dosage of the effect allele at each locus of genetic variants previously associated with blood pressure traits (systolic blood pressure GRS (GRSSBP): 554 variants; diastolic blood pressure GRS (GRSDBP): 481 variants; mean arterial pressure GRS (GRSMAP): 20 variants; pulse pressure GRS (GRSPP): 478 variants; hypertension GRS (GRSHTN): 22 variants; combined GRS (GRScomb): 1152 variants). Each GRS was longitudinally associated with its corresponding blood pressure trait, with estimated effects per GRS SD unit of 0.50 to 1.21 mm Hg for quantitative traits and odds ratios (ORs) of 1.10 to 1.35 for hypertension incidence traits. The GRScomb was also significantly associated with hypertension incidence defined according to European guidelines (OR, 1.22 per SD; 95% CI, 1.10‒1.35) but not US guidelines (OR, 1.11 per SD; 95% CI, 0.99‒1.25) while controlling for traditional risk factors. The addition of GRScomb to a model containing traditional risk factors only marginally improved discrimination (Δarea under the ROC curve = 0.001-0.002). Conclusions GRSs based on discovered blood pressure-associated variants are associated with long-term changes in blood pressure traits and hypertension incidence, but the inclusion of genetic factors in a model composed of conventional hypertension risk factors did not yield a material increase in predictive ability.

Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis.

The association between blood pressure (BP) and bladder cancer (BC) risk remains unclear with confounding by smoking being of particular concern. We investigated the association between BP and BC risk among men using conventional survival-analysis, and by Mendelian Randomization (MR) analysis in an attempt to disconnect the association from smoking. We additionally investigated the interaction between BP and N-acetyltransferase-2 (NAT2) rs1495741, an established BC genetic risk variant, in the association. Populations consisting of 188,167 men with 502 incident BC's in the UK-biobank and 27,107 men with 928 incident BC's in two Swedish cohorts were used for the analysis. We found a positive association between systolic BP and BC risk in Cox-regression survival analysis in the Swedish cohorts, (hazard ratio [HR] per standard deviation [SD]: 1.14 [95% confidence interval 1.05-1.22]) and MR analysis (odds ratio per SD: 2-stage least-square regression, 7.70 [1.92-30.9]; inverse-variance weighted estimate, 3.43 [1.12-10.5]), and no associations in the UK-biobank (HR systolic BP: 0.93 [0.85-1.02]; MR OR: 1.24 [0.35-4.40] and 1.37 [0.43-4.37], respectively). BP levels were positively associated with muscle-invasive BC (MIBC) (HRs: systolic BP, 1.32 [1.09-1.59]; diastolic BP, 1.27 [1.04-1.55]), but not with non-muscle invasive BC, which could be analyzed in the Swedish cohorts only. There was no interaction between BP and NAT2 in relation to BC on the additive or multiplicative scale. These results suggest that BP might be related to BC, more particularly MIBC. There was no evidence to support interaction between BP and NAT2 in relation to BC in our study.