Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases1,2, advances in genotyping and sequencing technology have made genome-wide association (GWA) studies an obvious general approach for studying the genetics of natural variation and traits of agricultural importance. They are particularly useful when inbred lines are available because once these lines have been genotyped, they can be phenotyped multiple times, making it possible (as well as extremely cost-effective) to study many different traits in many different environments, while replicating the phenotypic measurements to reduce environmental noise. Here we demonstrate the power of this approach by carrying out a GWA study of 107 phenotypes in Arabidopsis thaliana, a widely distributed, predominantly selfing model plant, known to harbor considerable genetic variation for many adaptively important traits3. Our results are dramatically different from those of human GWA studies in that we identify many common alleles with major effect, but they are also, in many cases, harder to interpret because confounding by complex genetics and population structure make it difficult to distinguish true from false associations. However, a priori candidates are significantly overrepresented among these associations as well, making many of them excellent candidates for follow-up experiments by the Arabidopsis community. Our study clearly demonstrates the feasibility of GWA studies in A. thaliana, and suggests that the approach will be appropriate for many other organisms.

Aims While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. Methods and results We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. Conclusions A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.

We performed gene-environment interaction genome-wide association analysis (G × E GWAS) to identify SNPs whose effects on metabolic traits are modified by chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis (MESA). In Whites, the G × E GWAS for hip circumference identified five SNPs within the Early B-cell Factor 1 (EBF1) gene, all of which were in strong linkage disequilibrium. The gene-by-stress interaction (SNP × STRESS) term P-values were genome-wide significant (Ps = 7.14E − 09 to 2.33E − 08, uncorrected; Ps = 1.99E − 07 to 5.18E − 07, corrected for genomic control). The SNP-only (without interaction) model P-values (Ps = 0.011-0.022) were not significant at the conventional genome-wide significance level. Further analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal-medial thickness (CCIMT), supporting a proposed model of gene-by-stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself. Structural equation path analysis suggested that the path from chronic psychosocial stress to CCIMT via hip circumference and fasting glucose was larger (estimate = 0.26, P = 0.033, 95% CI = 0.02-0.49) in the EBF1 rs4704963 CT/CC genotypes group than the same path in the TT group (estimate = 0.004, P = 0.34, 95% CI = − 0.004-0.012). We replicated the association of the EBF1 SNPs and hip circumference in the Framingham Offspring Cohort (gene-by-stress term P-values = 0.007-0.012) as well as identified similar path relationships. This observed and replicated interaction between psychosocial stress and variation in the EBF1 gene may provide a biological hypothesis for the complex relationship between psychosocial stress, central obesity, diabetes, and cardiovascular disease. INTRODUCTIONAlthough mortality attributable to cardiovascular disease (CVD) has declined in the United States, the burden of disease remains high. 1 It remains the leading cause of illness and death worldwide. Hypertension, obesity, dyslipidemia, insulin resistance and type II diabetes mellitus, and physical inactivity are among the eight risk factors that account for 61% of cardiovascular deaths. These same risk factors account for over three quarters of ischemic heart disease. 2 These risk factors are influenced by both environmental exposures and genetic background and the heritability of these risk factors can be as high as 77%, 3 making it difficult to clearly separate CVD risk factors into genetic and nongenetic categories. The INTERHEART study has evaluated the effect of both physical and psychosocial factors on the risk of myocardial infarction and has shown that a higher prevalence of psychological stress and other psychosocial factors like depression account for 34% of the population attributable risk for myocardial infarction, independently of physical risk factors. 4 The co-occ...

Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.

Objectives Examine the association between SES and C-reactive protein (CRP) to understand how SES may increase the risk of CVD and thus identify targets for prevention measures. Methods Path models were used to examine direct and indirect associations of four indices of SES (objective early life built environment ratings, parental and participant education, and income) with CRP measured during early adulthood using data from the Add Health Study (N=11,371, mean age 29, range 24–32 years; 53.8% women, 28.0% black participants). The present study examined potential mediation of the association of SES with CRP by way of body mass index [BMI], smoking, and alcohol consumption within White and Black males and females. Results BMI was a mediator of the relation between parent education and CRP for White males (path coefficient (γ) = −0.05, p<0.001) and females (γ = −0.05, p<0.001). Smoking mediated the income-CRP (γ = −0.01, p< 0.01) and the education-CRP (γ = −0.07, p< 0.001) relation for White males. BMI mediated the relation between all measures of SES and CRP for White females (γ ‘s between −0.02- and −0.05; p’s <0.01). None of the risk factors mediated the SES-CRP relation in Black participants. Conclusions These findings indicate that the association of SES with CRP are influenced by both the timing and type of SES measure examined. In addition, race and sex play a role in how BMI and smoking influence the SES-CRP relationship, such that both factors play a role in white males and BMI in white females.

Microflares are small activities in solar low atmosphere, some are in the low corona, and others in the chromosphere. Observations show that some of the microflares are triggered by magnetic reconnection between emerging flux and a pre-existing background magnetic field. We perform 2.5D compressible resistive MHD simulations of magnetic reconnection with gravity considered. The background magnetic field is a canopy-type configuration which is rooted at the boundary of the solar supergranule. By changing the bottom boundary conditions in the simulation, new magnetic flux emerges up at the center of the supergranule and reconnects with the canopy-type magnetic field. We successfully simulate the coronal and chromospheric microflares, whose current sheets are located at the corona and the chromosphere, respectively. The microflare of coronal origin has a bigger size and a higher temperature enhancement than that of chromospheric origin. In the microflares of coronal origin, we also found a hot jet (∼1.8×10 6 K), which is probably related to the observational EUV/SXR jets, and a cold jet (∼10 4 K), which is similar to the observational Hα/Ca surges, whereas there is only an Hα/Ca bright point in the microflares of chromospheric origin. The study of parameter dependence shows that the size and strength of the emerging magnetic flux are the key parameters which determine the height of the reconnection location, and further determine the different observational features of the microflares.

BackgroundPneumonia is common in children and mostly caused by many pathogens. The aim of this study was to investigate whether the incidence of pediatric mycoplasma pneumoniae (MP) pneumonia and respiratory syncytial virus (RSV) pneumonia was associated with meteorological factors in Hangzhou, China.MethodsA total of 36500 pneumonia patients were recruited to participate in the study. Nasopharyngeal swabs were collected for the detection of MP and RSV using real-time polymerase chain reaction (RT-PCR) and direct immunofluorescence (DIF) assays, respectively. We used a distributed lag non-linear model (DLNM) to evaluate the correlations between the MP/RSV incidence and meteorological factors.ResultsThe detection rates of MP and RSV were 18.4% and 10.4%, respectively. There was a positive correlation between temperature and the MP infection rate, but RSV infection rate was negatively associated with temperature. Moreover, the impact of temperature on infection with RSV presented evident lag and cumulative effects. There was also an evident lag effect of temperature on the infection rate of MP; however, there was no evident cumulative effect.ConclusionsIn this study, the results showed meteorological factors play an important role in the incidence of these two pathogens. All these results can provide the laboratory basis for the early diagnosis and treatment of pneumonia in children.

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