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Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease 总被引:1,自引:0,他引:1
Trynka G Hunt KA Bockett NA Romanos J Mistry V Szperl A Bakker SF Bardella MT Bhaw-Rosun L Castillejo G de la Concha EG de Almeida RC Dias KR van Diemen CC Dubois PC Duerr RH Edkins S Franke L Fransen K Gutierrez J Heap GA Hrdlickova B Hunt S Izurieta LP Izzo V Joosten LA Langford C Mazzilli MC Mein CA Midah V Mitrovic M Mora B Morelli M Nutland S Núñez C Onengut-Gumuscu S Pearce K Platteel M Polanco I Potter S Ribes-Koninckx C Ricaño-Ponce I Rich SS Rybak A Santiago JL Senapati S Sood A 《Nature genetics》2011,43(12):1193-1201
Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease. 相似文献
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Burdon KP Macgregor S Hewitt AW Sharma S Chidlow G Mills RA Danoy P Casson R Viswanathan AC Liu JZ Landers J Henders AK Wood J Souzeau E Crawford A Leo P Wang JJ Rochtchina E Nyholt DR Martin NG Montgomery GW Mitchell P Brown MA Mackey DA Craig JE 《Nature genetics》2011,43(6):574-578
We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. 相似文献
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The third Conference of the Parties in Kyoto set the target of reducing greenhouse-gas emissions by an average of 5.3% with respect to 1990 values by 2008-2012. One of the main objections to the protocol's ratification is that compliance would pose an unbearable economic burden on the countries involved. But we show here that this is not the case if costs apart from the direct costs of energy production are also considered. Costs are also incurred in rectifying damage to human health, material goods, agriculture and the environment related to greenhouse-gas emissions. 相似文献
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Number crunching vs. number theory: computers and FLT,from Kummer to SWAC (1850–1960), and beyond 总被引:1,自引:1,他引:0
Leo Corry 《Archive for History of Exact Sciences》2008,62(4):393-455
The present article discusses the computational tools (both conceptual and material) used in various attempts to deal with
individual cases of FLT, as well as the changing historical contexts in which these tools were developed and used, and affected
research. It also explores the changing conceptions about the role of computations within the overall disciplinary picture
of number theory, how they influenced research on the theorem, and the kinds of general insights thus achieved. After an overview
of Kummer’s contributions and its immediate influence, I present work that favored intensive computations of particular cases
of FLT as a legitimate, fruitful, and worth-pursuing number-theoretical endeavor, and that were part of a coherent and active,
but essentially low-profile tradition within nineteenth century number theory. This work was related to table making activity
that was encouraged by institutions and individuals whose motivations came mainly from applied mathematics, astronomy, and
engineering, and seldom from number theory proper. A main section of the article is devoted to the fruitful collaboration
between Harry S. Vandiver and Emma and Dick Lehmer. I show how their early work led to the hesitant introduction of electronic
computers for research related with FLT. Their joint work became a milestone for computer-assisted activity in number theory
at large. 相似文献
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Mutation in myosin heavy chain 6 causes atrial septal defect 总被引:23,自引:0,他引:23
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Jarillo-Herrero P Kong J van der Zant HS Dekker C Kouwenhoven LP De Franceschi S 《Nature》2005,434(7032):484-488
Progress in the fabrication of nanometre-scale electronic devices is opening new opportunities to uncover deeper aspects of the Kondo effect--a characteristic phenomenon in the physics of strongly correlated electrons. Artificial single-impurity Kondo systems have been realized in various nanostructures, including semiconductor quantum dots, carbon nanotubes and individual molecules. The Kondo effect is usually regarded as a spin-related phenomenon, namely the coherent exchange of the spin between a localized state and a Fermi sea of delocalized electrons. In principle, however, the role of the spin could be replaced by other degrees of freedom, such as an orbital quantum number. Here we show that the unique electronic structure of carbon nanotubes enables the observation of a purely orbital Kondo effect. We use a magnetic field to tune spin-polarized states into orbital degeneracy and conclude that the orbital quantum number is conserved during tunnelling. When orbital and spin degeneracies are present simultaneously, we observe a strongly enhanced Kondo effect, with a multiple splitting of the Kondo resonance at finite field and predicted to obey a so-called SU4 symmetry. 相似文献
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罗明高 《西南石油大学学报(自然科学版)》1992,14(3):9-13
本文对传统的石油地质理论定义的含油气面积提出了异议,用倒转背斜油气藏、断层下盘油气藏和不整合面下油气藏的实例阐明在传统定义下确定含油气面积存在的问题,指出用这种方法确定的含油气面积小于实际面积。笔者将含油气面积定义为含油气体在水平面上的投影区域,并推荐了三种正确的确定方法、 相似文献
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