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| 2. |
- 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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| 3. |
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- 2019
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Journal article (peer-reviewed)
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| 4. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 5. |
- Bellm, Eric C., et al.
(author)
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The Zwicky Transient Facility : System Overview, Performance, and First Results
- 2019
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In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
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Journal article (peer-reviewed)abstract
- The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
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| 6. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - 2050-084X. ; 5
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Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 7. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 8. |
- Sun, Xu, et al.
(author)
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Chinese Herbal Medicine as Adjunctive Therapy to Chemotherapy for Breast Cancer : A Systematic Review and Meta-Analysis
- 2016
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In: Evidence-based Complementary and Alternative Medicine. - : Hindawi Limited. - 1741-427X .- 1741-4288.
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Research review (peer-reviewed)abstract
- Chinese herbal medicine (CHM) has been increasingly employed during therapy for breast cancer, but its efficacy remains a matter of debate. This systematic review examined randomized controlled trials to provide a critical evaluation of this treatment. The results demonstrated that the combined use of CHM with chemotherapy may improve the immediate tumor response and reduce chemotherapy-associated adverse events. Our findings highlight the poor quality of Chinese studies, and additional well-designed randomized controlled trials addressing the role of CHM are warranted. The lack of molecular-based evidence for CHM and Zheng has resulted in a limited understanding and acceptance of CHM and traditional Chinese medicine in Western countries. We believe that researchers should immediately explore a CHM-based cure, and CHM should be applied to routine care as soon as conclusive data are available.
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| 9. |
- Wu, Ping-Hsun, et al.
(author)
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Exploring the Benefit of 2-Methylbutyric Acid in Patients Undergoing Hemodialysis Using a Cardiovascular Proteomics Approach
- 2019
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In: Nutrients. - : MDPI. - 2072-6643. ; 11:12
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Journal article (peer-reviewed)abstract
- Short-chain fatty acids (SCFAs) can reduce pro-inflammatory parameters and oxidative stress, providing potential cardiovascular (CV) benefits. Although some evidence links SCFAs with host metabolic health via several biological mechanisms, the role of SCFA on CV disease in patients with kidney disease remains unclear. Herein, we investigate the association between a SCFA, 2-methylbutyric acid, and target CV proteomics to explore the potential pathophysiology of SCFA-related CV benefit in patients with kidney disease. Circulating 2-methylbutyric acid was quantified by high-performance liquid chromatography and 181 CV proteins by a proximity extension assay in 163 patients undergoing hemodialysis (HD). The associations between 2-methylbutyric acid and CV proteins were evaluated using linear regression analysis with age and gender, and multiple testing adjustment. The selected CV protein in the discovery phase was further confirmed in multivariable-adjusted models and evaluated by continuous scale association. The mean value of circulating 2-methylbutyric acid was 0.22 +/- 0.02 mu m which was negatively associated with bone morphogenetic protein 6 (BMP-6) according to the false discovery rate (FDR) multiple testing adjustment method. The 2-methylbutyric acid level remained negatively associated with BMP-6 (beta coefficient -1.00, 95% confidence interval -1.45 to -0.55, p < 0.001) after controlling for other CV risk factors in multivariable models. The cubic spline curve demonstrated a linear relationship. In conclusion, circulating 2-methylbutyric acid level was negatively associated with BMP-6, suggesting that this pathway maybe involved in vascular health in patients undergoing HD. However, further in vitro work is still needed to validate the translation of the mechanistic pathways.
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| 10. |
- Yi-Ting, Lin, et al.
(author)
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Indole-3 acetic acid increased risk of impaired cognitive function in patients receiving hemodialysis
- 2019
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In: Neurotoxicology. - : Elsevier BV. - 0161-813X .- 1872-9711. ; 73, s. 85-91
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Journal article (peer-reviewed)abstract
- Patients receiving hemodialysis (HD) have a higher risk of cognitive impairment and dementia than the general population. The accumulation of uremic toxins in the brain causes uremic encephalopathy, however, limited data exists to elucidate the effect of protein-bound uremic toxins on cognitive function. Here we investigate the effect of indole-3 acetic acid (IAA) and hippuric acid (HA), two different protein-bound uremic toxins from amino acid derivatives, on cognitive function by Silico and in a clinical study. Prevalent HD patients were enrolled in two independent hospitals. Serum IAA and HA were measured using mass spectrometry. Cognitive performance was measured using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Cognitive Abilities Screening Instrument (CASI) by trained psychologists. Using silico data to predict the effect of blood-brain barrier penetration was performed. The silico data demonstrated that IAA and HA had positive blood-brain barrier penetration ability. Amongst the 230 HD patients, serum IAA was associated with poor MMSE score (beta = -0.90, 95% CI -1.61 to -0.19) and poor CASI score (beta = -3.29, 95% CI -5.69 to -0.88) in stepwise multiple linear regression analysis. In logistic regression model, Serum IAA was also associated with cognitive impairment based on MMSE definition (OR, 1.96, 95% CI 1.10, 3.5) and CASI definition (OR, 2.09, 95% CI 1.21, 3.61). There was no correlation between Serum HA levels and cognitive function status. In conclusion, IAA, not HA, was associated with cognitive impairment in HD patients. Further large scale and prospective studies are needed to confirm our findings.
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