| 1. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- Yoo, Taekyeong, et al.
(author)
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Disease-specific eQTL screening reveals an anti-fibrotic effect of AGXT2 in non-alcoholic fatty liver disease.
- 2021
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In: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 75:3, s. 514-523
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Journal article (peer-reviewed)abstract
- Nonalcoholic fatty liver disease (NAFLD) poses an impending clinical burden. Genome-wide association studies have revealed a limited contribution of genomic variants to the disease, requiring alternative but robust approaches to identify disease-associated variants and genes. We carried out a disease-specific expression quantitative trait loci (eQTL) screen to identify novel genetic factors that specifically act on NAFLD progression on the basis of genotype.We recruited 125 Korean biopsy-proven NAFLD patients and healthy individuals and performed eQTL analyses using 21,272 transcripts and 3,234,941 genotyped and imputed SNPs. We then selected eQTLs that were detected only in the NAFLD group, but not in the control group (i.e., NAFLD-eQTLs). An additional cohort of 162 Korean NAFLD individuals was used for replication. The function of the selected eQTL toward NAFLD development was validated using HepG2, primary hepatocytes and NAFLD mouse models.The NAFLD-specific eQTL screening yielded 242 loci. Among them, AGXT2, encoding alanine-glyoxylate aminotransferase 2, displayed decreased expression in NAFLD patients homozygous for the non-reference allele of rs2291702, compared to no-NAFLD subjects with the same genotype (P = 4.79 × 10-6). This change was replicated in an additional 162 individuals, yielding a combined P-value of 8.05 × 10-8 from a total of 245 NAFLD patients and 48 controls. Knockdown of AGXT2 induced palmitate-overloaded hepatocyte death by increasing ER stress, and exacerbated NAFLD diet-induced liver fibrosis in mice. However, overexpression of AGXT2 reversely attenuated liver fibrosis and steatosis as well.We implicate a new molecular role of AGXT2 in NAFLD. Our overall approach will serve as an efficient tool for uncovering novel genetic factors that contribute to liver steatosis and fibrosis in patients with NAFLD.Elucidating causal genes for NAFLD has been challenging due to limited tissue availability and the polygenic nature of the disease. Using liver and blood samples from 125 biopsy-proven NAFLD and no-NAFLD Korean individuals and an additional 162 individuals for replication, we devised a new analytic method to identify causal genes. Among the candidates, we found that AGXT2-rs2291702 protects against liver fibrosis in a genotype-dependent manner with the potential for therapeutic interventions. Our approach enables the discovery of NAFLD causal genes that act on the basis of genotype.
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| 3. |
- Choi, Hyeon-Seo, et al.
(author)
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Oriented Crystal Growth during Perovskite Surface Reconstruction
- 2022
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In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 14:45, s. 51149-51156
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Journal article (peer-reviewed)abstract
- Surface passivation has become a key strategy for an improvement in power conversion efficiency (PCE) of perovskite solar cells (PSCs) since PSCs experienced a steep increase in PCE and reached a comparably matured point. Recently, surface passivation using a mixed salt of fluorinated alkyl ammonium iodide and formamidinium bromide demon-strated a remarkable improvement in both performance and stability, which can be tuned by the length of the alkyl chain. Nevertheless, the role of the alkyl chain in manipulating surface-limited crystal growth was not fully understood, preventing a further progress in interface control. In this study, we found that the length of the fluorine-substituted alkyl chain governed the crystal formation dynamics by manipulating surface tensions of different crystal orientations. The overall enhancement of the (001) plane, being the most favored, commonly resulted from the surface reformation of the perovskite film regardless of the chain length, while the highly oriented (001) over (111) was monitored with a particular chain length. The enhanced crystal orientation during surface recrystallization was responsible for the low trap density and thus effectively suppressed charge recombination at the interface, resulting in a considerable increase in open-circuit voltage and fill factor.
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| 4. |
- Lee, Keum Hwa, et al.
(author)
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Consumption of Fish and omega-3 Fatty Acids and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies
- 2020
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In: ADVANCES IN NUTRITION. - : OXFORD UNIV PRESS. - 2161-8313 .- 2156-5376. ; 11:5, s. 1134-1149
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Research review (peer-reviewed)abstract
- Multiple studies have suggested that omega-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between omega-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or omega-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between omega-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta analyses by study design, we found weak associations between omega-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although omega-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between omega-3 fatty acid consumption and cancer risks.
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| 5. |
- Kim, Hyeri, et al.
(author)
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Toward Sustaining Bioplastics : Add a Pinch of Seasoning
- 2023
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In: ACS Sustainable Chemistry and Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 11:5, s. 1846-1856
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Journal article (peer-reviewed)abstract
- Modern society can no longer sustain accumulating plastic pollution without intervention; plastic waste has even found its way into the food that we consume. Unfortunately, biodegradable alternatives lack sound commercial and economic distinctiveness because mechanical strength and biodegradability are typically mutually exclusive. Inspired by fine cuisine, we introduce a novel synthetic method, referred to as “seasoning”, which consists of adding a minimal amount of a biobased multifunctional monomer to pinch the amorphous domains of poly(butylene succinate). Seasoning with only 0.03 mol % of a biobased monomer led to a significantly improved oxygen barrier, high strength (86 MPa), and excellent elongation at break (654%). To the best of our knowledge, this “seasoning” approach with the significant property improvement provided is unique in the bioplastics research field. The proposed approach is highly scalable, relies on existing industrial production, and has the potential to expand current biodegradable plastic applications through its simplicity.
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| 6. |
- Marras, Alessandro, et al.
(author)
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Percival : A soft x-ray imager for synchrotron rings and free electron lasers
- 2019
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In: AIP Conference Proceedings. - : American Institute of Physics (AIP). - 0094-243X. - 9780735417823
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Conference paper (peer-reviewed)abstract
- In this paper, we are presenting the Percival detector, a monolithic CMOS Imager for detection of soft x-rays in Synchrotron Rings and Free Electron Lasers. The imager consists in a 2D array of many (2M) small (27um pitch) pixels, without dead or blind zones in the imaging area. The imager achieves low noise and high dynamic range by means of an adaptive-gain in-pixel circuitry, that has been validated on prototypes. The imager features on-chip Analogue-to-Digital conversion to 12+1 bits, and has a readout speed which is compatible with most of Free Electron Laser Facilities. For direct detection of low-energy x-rays, the imager is back-illuminated and post-processed to achieve 100% fill factor.
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