Genome-Wide Association with Diabetes-Related Traits in the Framingham Heart Study

BACKGROUND: Susceptibility to type 2 diabetes may be conferred by genetic variants having modest effects on risk. Genome-wide fixed marker arrays offer a novel approach to detect these variants. METHODS: We used the Affymetrix 100K SNP array in 1,087 Framingham Offspring Study family members to examine genetic associations with three diabetes-related quantitative glucose traits (fasting plasma glucose (FPG), hemoglobin A1c, 28-yr time-averaged FPG (tFPG)), three insulin traits (fasting insulin, HOMA-insulin resistance, and 0–120 min insulin sensitivity index); and with risk for diabetes. We used additive generalized estimating equations (GEE) and family-based association test (FBAT) models to test associations of SNP genotypes with sex-age-age2-adjusted residual trait values, and Cox survival models to test incident diabetes. RESULTS: We found 415 SNPs associated (at p 1%) 100K SNPs in LD (r2 > 0.05) with ABCC8 A1369S (rs757110), KCNJ11 E23K (rs5219), or SNPs in CAPN10 or HNFa. PPARG P12A (rs1801282) was not significantly associated with diabetes or related traits. CONCLUSION: Framingham 100K SNP data is a resource for association tests of known and novel genes with diabetes and related traits posted at. Framingham 100K data replicate the TCF7L2 association with diabetes.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1); National Center for Research Resources General Clinical Research Center (M01-RR-01066); American Diabetes Association Career Developement Award; GlaxoSmithKline; Merck; Lilly; National Institutes of Health Research Career Award (K23 DK659678-03

Collaborative lifelong learning and professional transfer. Case study: ECO European Project

This research reviews the formative model of the sMOOCs (social MOOC) characterized by the interaction and the implication of the participants who, relying on collective intelligence, look for the co-creation of knowledge in every educational action. The fieldwork focuses on the analysis of the “Step by Step” sMOOC of ECO Project (the second and third editions), that aims at the training of e-teachers and the transfer of learning to the professional field. The research methodology is mixed, with quantitative and qualitative techniques: it uses a semi-structured questionnaire, in order to compare possible bivariate correlations between the different variables; it conducts a content analysis of the fragments of messages written by the participants in the forums of the course. One of the most significant conclusions is the high degree of satisfaction of the participants with regard to the value of the course for their professional life. This form of transfer of the learning process leads to the proposal of a new modality for MOOCs, the tMOOC as “transferMOOC”

A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study

<p>Abstract</p> <p>Background</p> <p>Glomerular filtration rate (GFR) and urinary albumin excretion (UAE) are markers of kidney function that are known to be heritable. Many endocrine conditions have strong familial components. We tested for association between the Affymetrix GeneChip Human Mapping 100K single nucleotide polymorphism (SNP) set and measures of kidney function and endocrine traits.</p> <p>Methods</p> <p>Genotype information on the Affymetrix GeneChip Human Mapping 100K SNP set was available on 1345 participants. Serum creatinine and cystatin-C (cysC; n = 981) were measured at the seventh examination cycle (1998–2001); GFR (n = 1010) was estimated via the Modification of Diet in Renal Disease (MDRD) equation; UAE was measured on spot urine samples during the sixth examination cycle (1995–1998) and was indexed to urinary creatinine (n = 822). Thyroid stimulating hormone (TSH) was measured at the third and fourth examination cycles (1981–1984; 1984–1987) and mean value of the measurements were used (n = 810). Age-sex-adjusted and multivariable-adjusted residuals for these measurements were used in association with genotype data using generalized estimating equations (GEE) and family-based association tests (FBAT) models. We presented the results for association tests using additive allele model. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg Equilibrium p-value ≥ 0.001, and call rates of at least 80%.</p> <p>Results</p> <p>The top SNPs associated with these traits using the GEE method were rs2839235 with GFR (p-value 1.6*10^-05), rs1158167 with cysC (p-value 8.5*10^-09), rs1712790 with UAE (p-value 1.9*10^-06), and rs6977660 with TSH (p-value 3.7*10^-06), respectively. The top SNPs associated with these traits using the FBAT method were rs6434804 with GFR(p-value 2.4*10^-5), rs563754 with cysC (p-value 4.7*10^-5), rs1243400 with UAE (p-value 4.8*10^-6), and rs4128956 with TSH (p-value 3.6*10^-5), respectively. Detailed association test results can be found at <url>http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007</url>. Four SNPs in or near the <it>CST</it>3 gene were highly associated with cysC levels (p-value 8.5*10^-09to 0.007).</p> <p>Conclusion</p> <p>Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.</p

Do insect outbreaks reduce the severity of subsequent forest fires?

Understanding the causes and consequences of rapid environmental change is an essential scientific frontier, particularly given the threat of climate- and land use-induced changes in disturbance regimes. In western North America, recent widespread insect outbreaks and wildfires have sparked acute concerns about potential insect-fire interactions. Although previous research shows that insect activity typically does not increase wildfire likelihood, key uncertainties remain regarding insect effects on wildfire severity (i.e., ecological impact). Recent assessments indicate that outbreak severity and burn severity are not strongly associated, but these studies have been limited to specific insect or fire events. Here, we present a regional census of large wildfire severity following outbreaks of two prevalent bark beetle and defoliator species, mountain pine beetle (Dendroctonus ponderosae) and western spruce budworm (Choristoneura freemani), across the US Pacific Northwest. We first quantify insect effects on burn severity with spatial modeling at the fire event scale and then evaluate how these effects vary across the full population of insect-fire events (n = 81 spanning 1987-2011). In contrast to common assumptions of positive feedbacks, we find that insects generally reduce the severity of subsequent wildfires. Specific effects vary with insect type and timing, but both insects decrease the abundance of live vegetation susceptible to wildfire at multiple time lags. By dampening subsequent burn severity, native insects could buffer rather than exacerbate fire regime changes expected due to land use and climate change. In light of these findings, we recommend a precautionary approach when designing and implementing forest management policies intended to reduce wildfire hazard and increase resilience to global change

Modelling of tungsten erosion and deposition in the divertor of JET-ILW in comparison to experimental findings

The erosion, transport and deposition of tungsten in the outer divertor of JET-ILW has been studied for an H-Mode discharge with low frequency ELMs. For this specific case with an inter-ELM electron temperature at the strike point of about 20 eV, tungsten sputtering between ELMs is almost exclusively due to beryllium impurity and self-sputtering. However, during ELMs tungsten sputtering due to deuterium becomes important and even dominates. The amount of simulated local deposition of tungsten relative to the amount of sputtered tungsten in between ELMs is very high and reaches values of 99% for an electron density of 5E13 cm(-3) at the strike point and electron temperatures between 10 and 30 eV. Smaller deposition values are simulated with reduced electron density. The direction of the B-field significantly influences the local deposition and leads to a reduction if the E x B drift directs towards the scrape-off-layer. Also, the thermal force can reduce the tungsten deposition, however, an ion temperature gradient of about 0.1 eV/mm or larger is needed for a significant effect. The tungsten deposition simulated during ELMs reaches values of about 98% assuming ELM parameters according to free-streaming model. The measured WI emission profiles in between and within ELMs have been reproduced by the simulation. The contribution to the overall net tungsten erosion during ELMs is about 5 times larger than the one in between ELMs for the studied case. However, this is due to the rather low electron temperature in between ELMs, which leads to deuterium impact energies below the sputtering threshold for tungsten.EURATOM 63305

Deuterium Balmer/Stark spectroscopy and impurity profiles: first results from mirror-link divertor spectroscopy system on the JET ITER-like wall

For the ITER-like wall, the JET mirror link divertor spectroscopy system was redesigned to fully cover the tungsten horizontal strike plate with faster time resolution and improved near-UV performance. Since the ITER-like wall project involves a change in JET from a carbon dominated machine to a beryllium and tungsten dominated machine with residual carbon, the aim of the system is to provide the recycling flux, equivalent, to the impinging deuterium ion flux, the impurity fluxes (C, Be, O) and tungsten sputtering fluxes and hence give information on the tungsten divertor source. In order to do this self-consistently, the system also needs to provide plasma characterization through the deuterium Balmer spectra measurements of electron density and temperature during high density. L-Mode results at the density limit from Stark broadening/line ratio analysis will be presented and compared to Langmuir probe profiles and 2D-tomography of low-n Balmer emission [1]. Comparison with other diagnostics will be vital for modelling attempts with the EDGE2D-EIRENE code[2] as the best possible data sets need to be provided to study detachment behaviour.Comment: 18 pages, 11 figure

Multilevel examination of diabetes in modernising China: what elements of urbanisation are most associated with diabetes?

Aims/hypothesis: The purpose of this study was to examine the association between urbanisation-related factors and diabetes prevalence in China. Methods: Anthropometry, fasting blood glucose (FBG) and community-level data were collected for 7,741 adults (18–90 years) across 217 communities and nine provinces in the 2009 China Health and Nutrition Survey to examine diabetes (FBG ≥7.0 mmol/l or doctor diagnosis). Sex-stratified multilevel models, clustered at the community and province levels and controlling for individual-level age and household income were used to examine the association between diabetes and: (1) a multicomponent urbanisation measure reflecting overall modernisation and (2) 12 separate components of urbanisation (e.g., population density, employment, markets, infrastructure and social factors). Results: Prevalent diabetes was higher in more-urbanised (men 12%; women 9%) vs less-urbanised (men 6%; women 5%) areas. In sex-stratified multilevel models adjusting for residential community and province, age and household income, there was a twofold higher diabetes prevalence in urban vs rural areas (men OR 2.02, 95% CI 1.47, 2.78; women, OR 1.94, 95% CI 1.35, 2.79). All urbanisation components were positively associated with diabetes, with variation across components (e.g. men, economic and income diversity, OR 1.42, 95% CI 1.20, 1.66; women, transportation infrastructure, OR 1.18, 95% CI 1.06, 1.32). Community-level variation in diabetes was comparatively greater for women (intraclass correlation [ICC] 0.03–0.05) vs men (ICC ≤0.01); province-level variation was greater for men (men 0.03–0.04; women 0.02). Conclusions/interpretation: Diabetes prevention and treatment efforts are needed particularly in urbanised areas of China. Community economic factors, modern markets, communications and transportation infrastructure might present opportunities for such efforts. Electronic supplementary material The online version of this article (doi:10.1007/s00125-012-2697-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Genetic Effect on Body Mass Index and Cardiovascular Disease Across Generations

BACKGROUND: Whether genetics contribute to the rising prevalence of obesity or its cardiovascular consequences in today\u27s obesogenic environment remains unclear. We sought to determine whether the effects of a higher aggregate genetic burden of obesity risk on body mass index (BMI) or cardiovascular disease (CVD) differed by birth year. METHODS: We split the FHS (Framingham Heart Study) into 4 equally sized birth cohorts (birth year before 1932, 1932 to 1946, 1947 to 1959, and after 1960). We modeled a genetic predisposition to obesity using an additive genetic risk score (GRS) of 941 BMI-associated variants and tested for GRS-birth year interaction on log-BMI (outcome) when participants were around 50 years old (N=7693). We repeated the analysis using a GRS of 109 BMI-associated variants that increased CVD risk factors (type 2 diabetes, blood pressure, total cholesterol, and high-density lipoprotein) in addition to BMI. We then evaluated whether the effects of the BMI GRSs on CVD risk differed by birth cohort when participants were around 60 years old (N=5493). RESULTS: Compared with participants born before 1932 (mean age, 50.8 yrs [2.4]), those born after 1960 (mean age, 43.3 years [4.5]) had higher BMI (median, 25.4 [23.3-28.0] kg/m CONCLUSIONS: The significant GRS-birth year interactions indicate that common genetic variants have larger effects on middle-age BMI and CVD risk in people born more recently. These findings suggest that the increasingly obesogenic environment may amplify the impact of genetics on the risk of obesity and possibly its cardiovascular consequences