排序方式: 共有21条查询结果,搜索用时 296 毫秒
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Suhre K Shin SY Petersen AK Mohney RP Meredith D Wägele B Altmaier E;CARDIoGRAM Deloukas P Erdmann J Grundberg E Hammond CJ de Angelis MH Kastenmüller G Köttgen A Kronenberg F Mangino M Meisinger C Meitinger T Mewes HW Milburn MV Prehn C Raffler J Ried JS Römisch-Margl W Samani NJ Small KS Wichmann HE Zhai G Illig T Spector TD Adamski J Soranzo N Gieger C 《Nature》2011,477(7362):54-60
Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research. 相似文献
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Richards JB Yuan X Geller F Waterworth D Bataille V Glass D Song K Waeber G Vollenweider P Aben KK Kiemeney LA Walters B Soranzo N Thorsteinsdottir U Kong A Rafnar T Deloukas P Sulem P Stefansson H Stefansson K Spector TD Mooser V 《Nature genetics》2008,40(11):1282-1284
We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 x 10(-15)). 相似文献
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A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21 总被引:14,自引:0,他引:14
van Heel DA Franke L Hunt KA Gwilliam R Zhernakova A Inouye M Wapenaar MC Barnardo MC Bethel G Holmes GK Feighery C Jewell D Kelleher D Kumar P Travis S Walters JR Sanders DS Howdle P Swift J Playford RJ McLaren WM Mearin ML Mulder CJ McManus R McGinnis R Cardon LR Deloukas P Wijmenga C 《Nature genetics》2007,39(7):827-829
We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease. 相似文献
5.
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants 总被引:2,自引:0,他引:2
Wellcome Trust Case Control Consortium;Australo-Anglo-American Spondylitis Consortium 《Nature genetics》2007,39(11):1329-1337
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases. 相似文献
6.
Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease 总被引:1,自引:0,他引:1
Fisher SA Tremelling M Anderson CA Gwilliam R Bumpstead S Prescott NJ Nimmo ER Massey D Berzuini C Johnson C Barrett JC Cummings FR Drummond H Lees CW Onnie CM Hanson CE Blaszczyk K Inouye M Ewels P Ravindrarajah R Keniry A Hunt S Carter M Watkins N Ouwehand W Lewis CM Cardon L;Wellcome Trust Case Control Consortium Lobo A Forbes A Sanderson J Jewell DP Mansfield JC Deloukas P Mathew CG Parkes M Satsangi J 《Nature genetics》2008,40(6):710-712
We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases. 相似文献
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de Bakker PI McVean G Sabeti PC Miretti MM Green T Marchini J Ke X Monsuur AJ Whittaker P Delgado M Morrison J Richardson A Walsh EC Gao X Galver L Hart J Hafler DA Pericak-Vance M Todd JA Daly MJ Trowsdale J Wijmenga C Vyse TJ Beck S Murray SS Carrington M Gregory S Deloukas P Rioux JD 《Nature genetics》2006,38(10):1166-1172
The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes. 相似文献
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An evaluation of HapMap sample size and tagging SNP performance in large-scale empirical and simulated data sets 总被引:7,自引:0,他引:7
Zeggini E Rayner W Morris AP Hattersley AT Walker M Hitman GA Deloukas P Cardon LR McCarthy MI 《Nature genetics》2005,37(12):1320-1322
A substantial investment has been made in the generation of large public resources designed to enable the identification of tag SNP sets, but data establishing the adequacy of the sample sizes used are limited. Using large-scale empirical and simulated data sets, we found that the sample sizes used in the HapMap project are sufficient to capture common variation, but that performance declines substantially for variants with minor allele frequencies of <5%. 相似文献
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Small KS Hedman AK Grundberg E Nica AC Thorleifsson G Kong A Thorsteindottir U Shin SY Richards HB;GIANT Consortium;MAGIC Investigators;DIAGRAM Consortium Soranzo N Ahmadi KR Lindgren CM Stefansson K Dermitzakis ET Deloukas P Spector TD McCarthy MI;MuTHER Consortium 《Nature genetics》2011,43(6):561-564
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Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility 总被引:14,自引:0,他引:14
Parkes M Barrett JC Prescott NJ Tremelling M Anderson CA Fisher SA Roberts RG Nimmo ER Cummings FR Soars D Drummond H Lees CW Khawaja SA Bagnall R Burke DA Todhunter CE Ahmad T Onnie CM McArdle W Strachan D Bethel G Bryan C Lewis CM Deloukas P Forbes A Sanderson J Jewell DP Satsangi J Mansfield JC;Wellcome Trust Case Control Consortium Cardon L Mathew CG 《Nature genetics》2007,39(7):830-832
A genome-wide association scan in individuals with Crohn's disease by the Wellcome Trust Case Control Consortium detected strong association at four novel loci. We tested 37 SNPs from these and other loci for association in an independent case-control sample. We obtained replication for the autophagy-inducing IRGM gene on chromosome 5q33.1 (replication P = 6.6 x 10(-4), combined P = 2.1 x 10(-10)) and for nine other loci, including NKX2-3, PTPN2 and gene deserts on chromosomes 1q and 5p13. 相似文献