| 1. |
- Flannick, Jason, et al.
(author)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Journal article (peer-reviewed)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 2. |
- Manning, Alisa, et al.
(author)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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In: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Journal article (peer-reviewed)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 3. |
- Chilkoor, Govinda, et al.
(author)
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Sustainability of renewable fuel infrastructure : a screening LCA case study of anticorrosive graphene oxide epoxy liners in steel tanks for the storage of biodiesel and its blends
- 2017
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In: Environmental Science. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 19:2, s. 141-153
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Journal article (peer-reviewed)abstract
- Biodiesel is a widely used fuel that meets the renewable fuel standards developed under Energy Policy Act of 2005. However, biodiesel is known to pose a series of abiotic and biotic corrosion risks to storage tanks. A typical practice (incumbent system) used to protect the tanks from the risks include: (i) coat the interior surface of the tank with solvent free epoxy (SFE) liner, and (ii) add a biocide in the tank. We present a screening-level, life cycle assessment study to evaluate and compare the environmental performance of graphene-oxide (GO)-epoxy (GOE) liner with the incumbent system. TRACI is used as an impact assessment tool to model midpoint environmental impacts for the ten categories: global warming potential (GWP, kg CO2 eq.); acidification potential (AP, kg SO2 eq.); potential human health damage impacts due to carcinogens (HH-CP, CTUh) and non-carcinogens (HH-NCP, CTUh); potential respiratory effects (REP, kg PM2.5 eq); eutrophication potential (EP, kg N eq); ozone depletion potential (ODP kg CFC-11 eq); ecotoxicity potential (ETXP, CTUe); smog formation potential (SFP kg O3 eq); and fossil fuel depletion potential (FFDP MJ surplus). The equivalent functional unit of the LCA study is designed to protect the 30 m2 of the interior surface (unalloyed steel sheet) of a 10,000 liters biodiesel tank against abiotic and biotic corrosion during its service life of 20 years. Overall, this LCA study highlights an improved environmental performance for the GOE liner compared to the incumbent system; GOE-liner system showed: 91% lower ODP impacts; 59% smaller for REP; 62% smaller for AP; 67-69% smaller for GWP and HH-CP; 72-76% smaller for EP, SFP, and FFDP; and 81-83% smaller for ETXP and HH-NCP categories. The scenario analysis study reveals that these potential impacts change by less than 15% when the GOE liners are functionalized with silanized-GO nanosheets or GO-reinforced, polyvinyl carbazole to improve the antimicrobial properties. The results from uncertainty analysis indicate that the impacts for the incumbent system are more sensitive to changes in key modeling parameters compared to that for GOE liner system.
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