Abstract:
:There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined approximately 2,000 individuals for each of 7 major diseases and a shared set of approximately 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 x 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals (including 58 loci with single-point P values between 10(-5) and 5 x 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.
journal_name
Naturejournal_title
Natureauthors
Wellcome Trust Case Control Consortium.doi
10.1038/nature05911subject
Has Abstractpub_date
2007-06-07 00:00:00pages
661-78issue
7145eissn
0028-0836issn
1476-4687pii
nature05911journal_volume
447pub_type
杂志文章,多中心研究相关文献
NATURE文献大全abstract::Thyroid hormones and retinoic acid function through nuclear receptors that belong to the steroid/thyroid-hormone receptor superfamily. Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) require auxiliary nuclear proteins for efficient DNA binding. Here we report that retinoid X receptors RXR alpha is o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/355441a0
更新日期:1992-01-30 00:00:00
abstract::About one-third of the carbon dioxide (CO(2)) released into the atmosphere as a result of human activity has been absorbed by the oceans, where it partitions into the constituent ions of carbonic acid. This leads to ocean acidification, one of the major threats to marine ecosystems and particularly to calcifying organ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10295
更新日期:2011-08-03 00:00:00
abstract::The complete knowledge of a quantum state allows the prediction of the probability of all possible measurement outcomes, a crucial step in quantum mechanics. It can be provided by tomographic methods which have been applied to atomic, molecular, spin and photonic states. For optical or microwave photons, standard tomo...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13821
更新日期:2014-10-30 00:00:00
abstract::The surfaces of Earth and Mars contain large bedrock canyons that were carved by catastrophic outburst floods. Reconstructing the magnitude of these canyon-forming floods is essential for understanding the ways in which floods modify planetary surfaces, the hydrology of early Mars and abrupt changes in climate. Flood ...
journal_title:Nature
pub_type: 信件
doi:10.1038/nature19817
更新日期:2016-10-13 00:00:00
abstract::When chemical reactions whose rate increases with the concentration of a product species are carried out in imperfectly mixed systems, a variety of complex behaviours can occur. These phenomena, which have relevance for biological processes as well, include chaotic and stochastic behaviour and selection of one final s...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/374321a0
更新日期:1995-03-23 00:00:00
abstract::Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or ho...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/415530a
更新日期:2002-01-31 00:00:00
abstract::The unusual helium-rich (type Ib) supernova SN 2005E is distinguished from all supernovae hitherto observed by its faint and rapidly fading light curve, prominent calcium lines in late-phase spectra and lack of any mark of recent star formation near the supernova location. These properties are claimed to be explained ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09055
更新日期:2010-05-20 00:00:00
abstract::Valuable information about proto-oncogenes and their physiological function has been obtained by studying their expression in normal cells. However, expression of the c-mos gene, the cellular homologue of the transforming gene of Moloney murine sarcoma virus, has not been detected in normal mouse cells or tissues. The...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/315516a0
更新日期:1985-06-06 00:00:00
abstract::The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago, only a few have been characterized with res...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09907
更新日期:2011-04-28 00:00:00
abstract::The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14236
更新日期:2015-02-26 00:00:00
abstract::Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children1,2, and genetic events that cooperate with known somatic dri...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2164-5
更新日期:2020-04-01 00:00:00
abstract::Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1631-3
更新日期:2019-11-01 00:00:00
abstract::Diatoms are one of the most ecologically successful classes of photosynthetic marine eukaryotes in the contemporary oceans. Over the past 30 million years, they have helped to moderate Earth's climate by absorbing carbon dioxide from the atmosphere, sequestering it via the biological carbon pump and ultimately burying...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14599
更新日期:2015-08-20 00:00:00
abstract::Epidermal growth factor (EGF) and transforming growth factor type I (TGF) are polypeptides of 53 and 50 amino acid residues, respectively. Both bind to EGF receptor, a 1,200-residue transmembranous glycoprotein, leading to phosphorylation of the receptor, enhancement of its tyrosine-specific kinase activity and ultima...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/313491a0
更新日期:1985-02-07 00:00:00
abstract::Inositol 1,4,5-trisphosphate (InsP3) can initiate calcium release into the cytoplasm in a variety of cells. From experiments using permeabilized cells, membrane vesicles, and patch-clamp techniques, it has been suggested that InsP3 acts by directly opening calcium channels. Here, we show that InsP3 induced openings of...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/336583a0
更新日期:1988-12-08 00:00:00
abstract::That animals and humans can accomplish the same goal using different effectors and different goals using the same effectors attests to the remarkable flexibility of the central nervous system. This phenomenon has been termed 'motor equivalence', an example being the writing of a name with a pencil held between the toe...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/33922
更新日期:1998-04-23 00:00:00
abstract::Members of the muscarinic acetylcholine receptor family (M1-M5) have central roles in the regulation of many fundamental physiological functions. Identifying the specific receptor subtype(s) that mediate the diverse muscarinic actions of acetylcholine is of considerable therapeutic interest, but has proved difficult p...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35065604
更新日期:2001-03-08 00:00:00
abstract::Measurements of the cosmic microwave background (CMB) radiation can reveal with remarkable precision the conditions of the Universe when it was approximately 400,000 years old. The three most fundamental properties of the CMB are its frequency spectrum (which determines the temperature), and the fluctuations in both t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01271
更新日期:2002-12-19 00:00:00
abstract::Despite the continued increase in atmospheric greenhouse gas concentrations, the annual-mean global temperature has not risen in the twenty-first century, challenging the prevailing view that anthropogenic forcing causes climate warming. Various mechanisms have been proposed for this hiatus in global warming, but thei...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/nature12534
更新日期:2013-09-19 00:00:00
abstract::Plants cope with the environment in a variety of ways, and ecological analyses attempt to capture this through life-history strategies or trait-based categorization. These approaches are limited because they treat the trade-off mechanisms that underlie plant responses as a black box. Approaches that involve the molecu...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature22010
更新日期:2017-03-15 00:00:00
abstract::A long-standing hypothesis on tumorigenesis is that cell division failure, generating genetically unstable tetraploid cells, facilitates the development of aneuploid malignancies. Here we test this idea by transiently blocking cytokinesis in p53-null (p53-/-) mouse mammary epithelial cells (MMECs), enabling the isolat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04217
更新日期:2005-10-13 00:00:00
abstract::Imperfect knowledge of the times at which 'snapshots' of a system are recorded degrades our ability to recover dynamical information, and can scramble the sequence of events. In X-ray free-electron lasers, for example, the uncertainty--the so-called timing jitter--between the arrival of an optical trigger ('pump') pul...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature17627
更新日期:2016-04-28 00:00:00
abstract::Recent work demonstrates that stochastic fluctuations in molecular populations have consequences for gene regulation. Previous experiments focused on noise sources or noise propagation through gene networks by measuring noise magnitudes. However, in theoretical analysis, we showed that noise frequency content is deter...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04194
更新日期:2006-02-02 00:00:00
abstract::Plasmacytoid dendritic cells (pDCs) sense viral and microbial DNA through endosomal Toll-like receptors to produce type 1 interferons. pDCs do not normally respond to self-DNA, but this restriction seems to break down in human autoimmune disease by an as yet poorly understood mechanism. Here we identify the antimicrob...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06116
更新日期:2007-10-04 00:00:00
abstract::As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0657-2
更新日期:2018-11-01 00:00:00
abstract::Grid cells provide a neural representation of space, by discharging when an animal traverses through the vertices of a periodic hexagonal grid spanning the environment. Although grid cells have been characterized in detail in rats, the fundamental question of what neural dynamics give rise to the grid structure remain...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10583
更新日期:2011-11-02 00:00:00
abstract::Mutations of the presenilin-1 gene are a major cause of familial early-onset Alzheimer's disease. Presenilin-1 can associate with members of the catenin family of signalling proteins, but the significance of this association is unknown. Here we show that presenilin-1 forms a complex with beta-catenin in vivo that incr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/27208
更新日期:1998-10-15 00:00:00
abstract::Birds can perceive the reflectance of ultraviolet light by biological structures. Here we show that the skin of the mouth and body of starling nestlings substantially reflects light in the ultraviolet range and that young in which this reflectance is reduced will gain less mass than controls, despite low background le...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/431262a
更新日期:2004-09-16 00:00:00
abstract::Unlike the electroweak sector of the standard model of particle physics, quantum chromodynamics (QCD) is surprisingly symmetric under time reversal. As there is no obvious reason for QCD being so symmetric, this phenomenon poses a theoretical problem, often referred to as the strong CP problem. The most attractive sol...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature20115
更新日期:2016-11-03 00:00:00
abstract::NADH oxidation in the respiratory chain is coupled to ion translocation across the membrane to build up an electrochemical gradient. The sodium-translocating NADH:quinone oxidoreductase (Na(+)-NQR), a membrane protein complex widespread among pathogenic bacteria, consists of six subunits, NqrA, B, C, D, E and F. To ou...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14003
更新日期:2014-12-04 00:00:00