Abstract:
:Gene-environment associations are important in rheumatoid arthritis (RA) susceptibility, with an association existing between smoking, HLA- DRB1 'shared epitope' alleles, PTPN22 and antibodies to cyclic citrullinated peptides (CCP). Here, we test the hypothesis that a subset of the anti-CCP response, with specific autoimmunity to citrullinated alpha-enolase, accounts for an important portion of these associations. In 1,497 individuals from three RA cohorts, antibodies to the immunodominant citrullinated alpha-enolase CEP-1 epitope were detected in 43-63% of the anti-CCP-positive individuals, and this subset was preferentially linked to HLA-DRB1*04. In a case-control analysis of 1,000 affected individuals and 872 controls, the combined effect of shared epitope, PTPN22 and smoking showed the strongest association with the anti-CEP-1-positive subset (odds ratio (OR) of 37, compared to an OR of 2 for the corresponding anti-CEP-1-negative, anti-CCP-positive subset). We conclude that citrullinated alpha-enolase is a specific citrullinated autoantigen that links smoking to genetic risk factors in the development of RA.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Mahdi H,Fisher BA,Källberg H,Plant D,Malmström V,Rönnelid J,Charles P,Ding B,Alfredsson L,Padyukov L,Symmons DP,Venables PJ,Klareskog L,Lundberg Kdoi
10.1038/ng.480subject
Has Abstractpub_date
2009-12-01 00:00:00pages
1319-24issue
12eissn
1061-4036issn
1546-1718pii
ng.480journal_volume
41pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::Dilated cardiomyopathy (DCM) is a highly heterogeneous trait with sarcomeric gene mutations predominating. The cause of a substantial percentage of DCMs remains unknown, and no gene-specific therapy is available. On the basis of resequencing of 513 DCM cases and 1,150 matched controls from various cohorts of distinct ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2963
更新日期:2014-06-01 00:00:00
abstract::Translocation events are frequent in cancer and may create chimeric fusions or 'regulatory rearrangements' that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3502
更新日期:2016-03-01 00:00:00
abstract::The plant circadian clock is a complex network of genes crucial for plant survival. A new study finds that domestication gradually slowed down the circadian clock of tomato via selection on two major genes-one that delayed phasing of the clock with daylight, whereas the other induced a longer period. ...
journal_title:Nature genetics
pub_type: 评论,杂志文章
doi:10.1038/ng.3476
更新日期:2016-01-01 00:00:00
abstract::To test the hypothesis that the human genome project will uncover many genes not previously discovered by sequencing of expressed sequence tags (ESTs), we designed and produced a set of microarrays using probes based on open reading frames (ORFs) in 350 Mb of finished and draft human sequence. Our approach aims to ide...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/81613
更新日期:2000-11-01 00:00:00
abstract::We conducted a meta-analysis of genome-wide association data to detect genes influencing age at menarche in 17,510 women. The strongest signal was at 9q31.2 (P = 1.7 × 10(-9)), where the nearest genes include TMEM38B, FKTN, FSD1L, TAL2 and ZNF462. The next best signal was near the LIN28B gene (rs7759938; P = 7.0 × 10(...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.386
更新日期:2009-06-01 00:00:00
abstract::Genetic recombination is a major force driving the evolution of many viruses. Recombination between two copackaged retroviral genomes may occur at rates as high as 40% per replication cycle. This enables genetic information to be shuffled rapidly, leading to recombinants with new patterns of mutations and phenotypes. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/78132
更新日期:2000-08-01 00:00:00
abstract::The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Hand1 is expressed in extraembryonic membranes, whereas Han...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0398-266
更新日期:1998-03-01 00:00:00
abstract::Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is r...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1997
更新日期:2007-04-01 00:00:00
abstract::Small nucleolar RNAs (snoRNAs) are conserved noncoding RNAs best studied as ribonucleoprotein (RNP) guides in RNA modification. To explore their role in cancer, we compared 5,473 tumor-normal genome pairs to identify snoRNAs with frequent copy number loss. The SNORD50A-SNORD50B snoRNA locus was deleted in 10-40% of 12...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3452
更新日期:2016-01-01 00:00:00
abstract::Differences in three-dimensional (3D) chromatin architecture can influence the integrity of topologically associating domains (TADs) and rewire specific enhancer-promoter interactions, impacting gene expression and leading to human disease. Here we investigate the 3D chromatin architecture in T cell acute lymphoblasti...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-020-0602-9
更新日期:2020-04-01 00:00:00
abstract::Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide asso...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.102
更新日期:2008-04-01 00:00:00
abstract::Haematopoietic development is regulated by nuclear protein complexes that coordinate lineage-specific patterns of gene expression. Targeted mutagenesis in embryonic stem cells and mice has revealed roles for the X-linked gene Gata1 in erythrocyte and megakaryocyte differentiation. GATA-1 is the founding member of a fa...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/73480
更新日期:2000-03-01 00:00:00
abstract::We report the 207-Mb genome sequence of the North American Arabidopsis lyrata strain MN47 based on 8.3× dideoxy sequence coverage. We predict 32,670 genes in this outcrossing species compared to the 27,025 genes in the selfing species Arabidopsis thaliana. The much smaller 125-Mb genome of A. thaliana, which diverged ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.807
更新日期:2011-05-01 00:00:00
abstract::The rate at which allelic diversity at the HLA loci evolves has been the subject of considerable controversy. The patchwork pattern of sequence polymorphism within the second exon of the HLA class II loci, particularly in the DPB1 locus, may have been generated by segmental exchange (gene conversion). We have analysed...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0895-407
更新日期:1995-08-01 00:00:00
abstract::Studies in experimental systems have identified a multitude of mutational mechanisms including DNA replication infidelity and DNA damage followed by inefficient repair or replicative bypass. However, the relative contributions of these mechanisms to human germline mutation remain unknown. Here, we show that error-pron...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-018-0285-7
更新日期:2019-01-01 00:00:00
abstract::A highly invasive form of non-typhoidal Salmonella (iNTS) disease has recently been documented in many countries in sub-Saharan Africa. The most common Salmonella enterica serovar causing this disease is Typhimurium (Salmonella Typhimurium). We applied whole-genome sequence-based phylogenetic methods to define the pop...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2423
更新日期:2012-11-01 00:00:00
abstract::The past decade has seen great advances in unraveling the biological basis of hereditary ataxias. Molecular studies of spinocerebellar ataxias (SCA) have extended our understanding of dominant ataxias. Causative genes have been identified for a few autosomal recessive ataxias: Friedreich's ataxia, ataxia with vitamin ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1927
更新日期:2007-01-01 00:00:00
abstract::Human synovial sarcomas contain a recurrent and specific chromosomal translocation t(X;18)(p11.2;q11.2). By screening a synovial sarcoma cDNA library with a yeast artificial chromosome spanning the X chromosome breakpoint, we have identified a hybrid transcript that contains 5' sequences (designated SYT) mapping to ch...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0894-502
更新日期:1994-08-01 00:00:00
abstract::Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing b...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3878
更新日期:2017-07-01 00:00:00
abstract::The organophosphate cholinesterase inhibitor paraoxon is hydrolysed by serum paraoxonase/arylesterase. A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning. We demonstrate that arginine at positi...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0193-73
更新日期:1993-01-01 00:00:00
abstract::Genomic and proteomic approaches can provide hypotheses concerning function for the large number of genes predicted from genome sequences. Because of the artificial nature of the assays, however, the information from these high-throughput approaches should be considered with caution. Although it is possible that more ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng776
更新日期:2001-12-01 00:00:00
abstract::Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine tract in ataxin-1. In affected neurons of SCA1 patients and transgenic mice, mutant ataxin-1 accumulates in a single, ubiquitin-positive nuclear inclusion. In this study, we show that these i...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/502
更新日期:1998-06-01 00:00:00
abstract::Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (ca...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.670
更新日期:2010-11-01 00:00:00
abstract::The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleot...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1479
更新日期:2004-12-01 00:00:00
abstract::Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal su...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1168
更新日期:2003-06-01 00:00:00
abstract::In the version of this article originally published, a box was misplaced in Fig. 1. The error has been corrected in the HTML and PDF versions of the article. ...
journal_title:Nature genetics
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41588-018-0137-5
更新日期:2018-08-01 00:00:00
abstract::The mammalian homeobox transcription factor CDX2 has key roles in intestinal development and differentiation. Heterozygous Cdx2 mice develop one or two benign hamartomas in the proximal colon, whereas heterozygous Apc(Delta716) mice develop numerous adenomatous polyps, mostly in the small intestine. Here we show that ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1265
更新日期:2003-12-01 00:00:00
abstract::The Human Genome Project and its spin-offs are making it increasingly feasible to determine the genetic basis of complex traits using genome-wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1582
更新日期:2005-07-01 00:00:00
abstract::Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six dis...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/88925
更新日期:2001-06-01 00:00:00
abstract::We identified homozygous truncating mutations in HOXA1 in three genetically isolated human populations. The resulting phenotype includes horizontal gaze abnormalities, deafness, facial weakness, hypoventilation, vascular malformations of the internal carotid arteries and cardiac outflow tract, mental retardation and a...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1636
更新日期:2005-10-01 00:00:00