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Genetically driven adiposity traits increase the risk of coronary artery disease independent of blood pressure, dyslipidaemia, glycaemic traits.

ABSTRACT: Adiposity has been associated with the risk of coronary artery disease (CAD) in observational studies, but their association may differ according to specific characteristics of studies. In Mendelian randomization (MR) analyses, genetic variants are used as instrumental variables (IVs) of exposures to examine causal effects to overcome confounding factors and reverse causation. We performed MR analyses for adiposity (n?=?322,154) on risk of CAD (60,801 cases and 123,504 controls) based on the currently largest genome-wide association studies. The estimated associations between adiposity traits and CAD were calculated by an inverse-variance weighted method with and without excluding the IVs, which are associated with the well-known risk factors of CAD. Genetic variants are identified to be associated with the well-known risk factors of CAD by a cross-phenotype meta-analysis method. Our results furnished strong evidence for a causal role of adiposity in risk of CAD, with the odds ratios (ORs) for CAD being 1.53 (95% CI 1.36-1.72) for body mass index (BMI), 1.48 (1.20-1.96) for waist-hip ratio (WHR), and 1.34 (1.07-1.59) for WHR adjusted for BMI (WHRadjBMI), respectively. After excluding mediators-associated IVs from the MR analyses, the corresponding ORs were 1.46 (1.28-1.67) for BMI, 1.39 (1.01-1.93) for WHR, and 1.38 (1.04-1.84) for WHRadjBMI, respectively. Furthermore, our results suggested that central adiposity and general adiposity might pose a similar risk for CAD. In summary, our data supported that genetically driven adiposity traits imposed the risk of CAD independent of blood pressure, dyslipidaemia, glycaemic traits, and type 2 diabetes.

SUBMITTER: Lv WQ

PROVIDER: S-EPMC6138729 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Genetically driven adiposity traits increase the risk of coronary artery disease independent of blood pressure, dyslipidaemia, glycaemic traits.

Lv Wan-Qiang WQ Zhang Xue X Fan Kun K Xia Xin X Zhang Qiang Q Liu Hui-Min HM Jiang Bu-Ying BY Zhang Wei-Dong WD Deng Hong-Wen HW

European journal of human genetics : EJHG 20180611 10

Adiposity has been associated with the risk of coronary artery disease (CAD) in observational studies, but their association may differ according to specific characteristics of studies. In Mendelian randomization (MR) analyses, genetic variants are used as instrumental variables (IVs) of exposures to examine causal effects to overcome confounding factors and reverse causation. We performed MR analyses for adiposity (n = 322,154) on risk of CAD (60,801 cases and 123,504 controls) based on the cur ...[more]

PMID: 29891878

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Project description:Background Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. Methods and Results In this study, we used 4 different genetic risk scores (GRS; GRS-BMI565, GRS-WHR324, GRS-VAT208, GRS-BF81) including hundreds of single nucleotide polymorphisms associated with body mass index, waist-to-hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban-based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive 795Projects were used to obtain genetic association estimates with blood pressure (BP). In both the Malmö Preventive Projects and Malmö Diet and Cancer studies, except for that for body fat, all of the genetic risk scores were significantly associated with systolic BP and diastolic BP, but with different magnitudes. In particular, in both cohorts, each standard deviation increase in the genetic risk score made up by the 324 single nucleotide polymorphisms associated with waist-to-hip ratio was associated with doubling of the likelihood of hypertension prevalence at baseline. However, only the genetic risk score made up by the 565 SNPs associated with body mass index was significantly associated with hypertension incidence during 23.6±4.3 years of follow-up in the Malmö Preventive Project. Conclusions We support a causal link between genetically mediated adiposity, especially waist-to-hip ratio and body mass index, and BP traits including hypertension prevalence and, for the first time to our knowledge, hypertension incidence. The differences in magnitude between these associations might suggest different mechanisms by which different adiposity affects BP/hypertension and consequently may indicate that tailored interventions are needed to reduce cardiovascular risk.

Project description:Flowers are critical for successful reproduction and have been a major axis of diversification among angiosperms. As the frequency and severity of droughts are increasing globally, maintaining water balance of flowers is crucial for food security and other ecosystem services that rely on flowering. Yet remarkably little is known about the hydraulic strategies of flowers. We characterized hydraulic strategies of leaves and flowers of ten species by combining anatomical observations using light and scanning electron microscopy with measurements of hydraulic physiology (minimum diffusive conductance (gmin) and pressure-volume (PV) curves parameters). We predicted that flowers would exhibit higher gmin and higher hydraulic capacitance than leaves, which would be associated with differences in intervessel pit traits because of their different hydraulic strategies. We found that, compared to leaves, flowers exhibited: 1) higher gmin, which was associated with higher hydraulic capacitance (CT); 2) lower variation in intervessel pit traits and differences in pit membrane area and pit aperture shape; and 3) independent coordination between intervessel pit traits and other anatomical and physiological traits; 4) independent evolution of most traits in flowers and leaves, resulting in 5) large differences in the regions of multivariate trait space occupied by flowers and leaves. Furthermore, across organs intervessel pit trait variation was orthogonal to variation in other anatomical and physiological traits, suggesting that pit traits represent an independent axis of variation that have as yet been unquantified in flowers. These results suggest that flowers, employ a drought-avoidant strategy of maintaining high capacitance that compensates for their higher gmin to prevent excessive declines in water potentials. This drought-avoidant strategy may have relaxed selection on intervessel pit traits and allowed them to vary independently from other anatomical and physiological traits. Furthermore, the independent evolution of floral and foliar anatomical and physiological traits highlights their modular development despite being borne from the same apical meristem.

Project description:BackgroundFew studies have developed risk models for dyslipidaemia, especially for rural populations. Furthermore, the performance of genetic factors in predicting dyslipidaemia has not been explored. The purpose of this study is to develop and evaluate prediction models with and without genetic factors for dyslipidaemia in rural populations.MethodsA total of 3596 individuals from the Henan Rural Cohort Study were included in this study. According to the ratio of 7:3, all individuals were divided into a training set and a testing set. The conventional models and conventional+GRS (genetic risk score) models were developed with Cox regression, artificial neural network (ANN), random forest (RF), and gradient boosting machine (GBM) classifiers in the training set. The area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination index (IDI) were used to assess the discrimination ability of the models, and the calibration curve was used to show calibration ability in the testing set.ResultsCompared to the lowest quartile of GRS, the hazard ratio (HR) (95% confidence interval (CI)) of individuals in the highest quartile of GRS was 1.23(1.07, 1.41) in the total population. Age, family history of diabetes, physical activity, body mass index (BMI), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to develop the conventional models, and the AUCs of the Cox, ANN, RF, and GBM classifiers were 0.702(0.673, 0.729), 0.736(0.708, 0.762), 0.787 (0.762, 0.811), and 0.816(0.792, 0.839), respectively. After adding GRS, the AUCs increased by 0.005, 0.018, 0.023, and 0.015 with the Cox, ANN, RF, and GBM classifiers, respectively. The corresponding NRI and IDI were 25.6, 7.8, 14.1, and 18.1% and 2.3, 1.0, 2.5, and 1.8%, respectively.ConclusionGenetic factors could improve the predictive ability of the dyslipidaemia risk model, suggesting that genetic information could be provided as a potential predictor to screen for clinical dyslipidaemia.Trial registrationThe Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register. (Trial registration: ChiCTR-OOC-15006699 . Registered 6 July 2015 - Retrospectively registered).

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Genetically driven adiposity traits increase the risk of coronary artery disease independent of blood pressure, dyslipidaemia, glycaemic traits.

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Genetically driven adiposity traits increase the risk of coronary artery disease independent of blood pressure, dyslipidaemia, glycaemic traits.

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