共查询到20条相似文献,搜索用时 31 毫秒
1.
2.
The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke 总被引:29,自引:0,他引:29
Helgadottir A Manolescu A Thorleifsson G Gretarsdottir S Jonsdottir H Thorsteinsdottir U Samani NJ Gudmundsson G Grant SF Thorgeirsson G Sveinbjornsdottir S Valdimarsson EM Matthiasson SE Johannsson H Gudmundsdottir O Gurney ME Sainz J Thorhallsdottir M Andresdottir M Frigge ML Topol EJ Kong A Gudnason V Hakonarson H Gulcher JR Stefansson K 《Nature genetics》2004,36(3):233-239
We mapped a gene predisposing to myocardial infarction to a locus on chromosome 13q12-13. A four-marker single-nucleotide polymorphism (SNP) haplotype in this locus spanning the gene ALOX5AP encoding 5-lipoxygenase activating protein (FLAP) is associated with a two times greater risk of myocardial infarction in Iceland. This haplotype also confers almost two times greater risk of stroke. Another ALOX5AP haplotype is associated with myocardial infarction in individuals from the UK. Stimulated neutrophils from individuals with myocardial infarction produce more leukotriene B4, a key product in the 5-lipoxygenase pathway, than do neutrophils from controls, and this difference is largely attributed to cells from males who carry the at-risk haplotype. We conclude that variants of ALOX5AP are involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall. 相似文献
3.
A comprehensive linkage analysis for myocardial infarction and its related risk factors 总被引:24,自引:0,他引:24
Broeckel U Hengstenberg C Mayer B Holmer S Martin LJ Comuzzie AG Blangero J Nürnberg P Reis A Riegger GA Jacob HJ Schunkert H 《Nature genetics》2002,30(2):210-214
Coronary artery disease and myocardial infarction (MI) are leading causes of death in the western world. Numerous studies have shown that risk factors such as diabetes mellitus, arterial hypertension and hypercholesterolemia contribute to the development of the disease. Although each risk factor by itself is partly under genetic control, a positive family history is an independent predictor, which suggests that there are additional susceptibility genes. We have scanned the whole genome in 513 families to identify chromosomal regions linked to myocardial infarction and related risk factors that are known to be under genetic control. Here we show, by using variance component analysis and incorporating risk factors, that risk of myocardial infarction maps to a single region on chromosome 14 with a significant lod score of 3.9 (pointwise P=0.00015, genome-wide P<0.05), providing evidence of a principal MI locus. To characterize this locus we analyzed each risk factor by itself. Serum concentrations of lipoprotein (a) show linkage to both the apolipoprotein (a) locus (lod score 26.99) and a new locus on chromosome 1 (lod score 3.8). There is suggestive linkage for diabetes mellitus on chromosome 6 (lod score 2.96), for hypertension on chromosomes 1 and 6, for high-density and low-density lipoprotein cholesterol on chromosomes 1 and 17, and for triglyceride concentrations on chromosome 9. Although some of these risk factors overlap with previously identified loci, none overlaps with the newly identified susceptibility locus for myocardial infarction and coronary artery disease. 相似文献
4.
Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility 总被引:25,自引:0,他引:25
Wang X Ria M Kelmenson PM Eriksson P Higgins DC Samnegård A Petros C Rollins J Bennet AM Wiman B de Faire U Wennberg C Olsson PG Ishii N Sugamura K Hamsten A Forsman-Semb K Lagercrantz J Paigen B 《Nature genetics》2005,37(4):365-372
Ath1 is a quantitative trait locus on mouse chromosome 1 that renders C57BL/6 mice susceptible and C3H/He mice resistant to diet-induced atherosclerosis. The quantitative trait locus region encompasses 11 known genes, including Tnfsf4 (also called Ox40l or Cd134l), which encodes OX40 ligand. Here we report that mice with targeted mutations of Tnfsf4 had significantly (P 相似文献
5.
Helgadottir A Manolescu A Helgason A Thorleifsson G Thorsteinsdottir U Gudbjartsson DF Gretarsdottir S Magnusson KP Gudmundsson G Hicks A Jonsson T Grant SF Sainz J O'Brien SJ Sveinbjornsdottir S Valdimarsson EM Matthiasson SE Levey AI Abramson JL Reilly MP Vaccarino V Wolfe ML Gudnason V Quyyumi AA Topol EJ Rader DJ Thorgeirsson G Gulcher JR Hakonarson H Kong A Stefansson K 《Nature genetics》2006,38(1):68-74
Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group. 相似文献
6.
Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis 总被引:17,自引:0,他引:17
Gregory SG Schmidt S Seth P Oksenberg JR Hart J Prokop A Caillier SJ Ban M Goris A Barcellos LF Lincoln R McCauley JL Sawcer SJ Compston DA Dubois B Hauser SL Garcia-Blanco MA Pericak-Vance MA Haines JL;Multiple Sclerosis Genetics Group 《Nature genetics》2007,39(9):1083-1091
Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor alpha chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9 x 10(-7)). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer. 相似文献
7.
A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans 总被引:27,自引:0,他引:27
Prokunina L Castillejo-López C Oberg F Gunnarsson I Berg L Magnusson V Brookes AJ Tentler D Kristjansdóttir H Gröndal G Bolstad AI Svenungsson E Lundberg I Sturfelt G Jönssen A Truedsson L Lima G Alcocer-Varela J Jonsson R Gyllensten UB Harley JB Alarcón-Segovia D Steinsson K Alarcón-Riquelme ME 《Nature genetics》2002,32(4):666-669
8.
An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis 总被引:25,自引:0,他引:25
Tokuhiro S Yamada R Chang X Suzuki A Kochi Y Sawada T Suzuki M Nagasaki M Ohtsuki M Ono M Furukawa H Nagashima M Yoshino S Mabuchi A Sekine A Saito S Takahashi A Tsunoda T Nakamura Y Yamamoto K 《Nature genetics》2003,35(4):341-348
9.
Kubo M Hata J Ninomiya T Matsuda K Yonemoto K Nakano T Matsushita T Yamazaki K Ohnishi Y Saito S Kitazono T Ibayashi S Sueishi K Iida M Nakamura Y Kiyohara Y 《Nature genetics》2007,39(2):212-217
Cerebral infarction is the most common type of stroke and often causes long-term disability. To investigate the genetic contribution to cerebral infarction, we conducted a case-control study using 52,608 gene-based tag SNPs selected from the JSNP database. Here we report that a nonsynonymous SNP in a member of protein kinase C (PKC) family, PRKCH, was significantly associated with lacunar infarction in two independent Japanese samples (P = 5.1 x 10(-7), crude odds ratio of 1.40). This SNP is likely to affect PKC activity. Furthermore, a 14-year follow-up cohort study in Hisayama (Fukuoka, Japan) supported involvement of this SNP in the development of cerebral infarction (P = 0.03, age- and sex-adjusted hazard ratio of 2.83). We also found that PKCeta was expressed mainly in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions, and its expression increased as the lesion type progressed. Our results support a role for PRKCH in the pathogenesis of cerebral infarction. 相似文献
10.
11.
Wang F Xu CQ He Q Cai JP Li XC Wang D Xiong X Liao YH Zeng QT Yang YZ Cheng X Li C Yang R Wang CC Wu G Lu QL Bai Y Huang YF Yin D Yang Q Wang XJ Dai DP Zhang RF Wan J Ren JH Li SS Zhao YY Fu FF Huang Y Li QX Shi SW Lin N Pan ZW Li Y Yu B Wu YX Ke YH Lei J Wang N Luo CY Ji LY Gao LJ Li L Liu H Huang EW Cui J Jia N Ren X Li H Ke T Zhang XQ Liu JY Liu MG Xia H Yang B Shi LS Xia YL Tu X Wang QK 《Nature genetics》2011,43(4):345-349
Coronary artery disease (CAD) causes more than 700,000 deaths each year in China. Previous genome-wide association studies (GWAS) in populations of European ancestry identified several genetic loci for CAD, but no such study has yet been reported in the Chinese population. Here we report a three-stage GWAS in the Chinese Han population. We identified a new association between rs6903956 in a putative gene denoted as C6orf105 on chromosome 6p24.1 and CAD (P = 5.00 × 10?3, stage 2 validation; P = 3.00 × 10?3, P = 1.19 × 10?? and P = 4.00 × 10?3 in three independent stage 3 replication populations; P = 4.87 × 10?12, odds ratio = 1.51 in the combined population). The minor risk allele A of rs6903956 is associated with decreased C6orf105 mRNA expression. We report the first GWAS for CAD in the Chinese Han population and identify a SNP, rs6903956, in C6orf105 associated with susceptibility to CAD in this population. 相似文献
12.
Helgason A Pálsson S Thorleifsson G Grant SF Emilsson V Gunnarsdottir S Adeyemo A Chen Y Chen G Reynisdottir I Benediktsson R Hinney A Hansen T Andersen G Borch-Johnsen K Jorgensen T Schäfer H Faruque M Doumatey A Zhou J Wilensky RL Reilly MP Rader DJ Bagger Y Christiansen C Sigurdsson G Hebebrand J Pedersen O Thorsteinsdottir U Gulcher JR Kong A Rotimi C Stefánsson K 《Nature genetics》2007,39(2):218-225
13.
14.
Sun J Zheng SL Wiklund F Isaacs SD Purcell LD Gao Z Hsu FC Kim ST Liu W Zhu Y Stattin P Adami HO Wiley KE Dimitrov L Sun J Li T Turner AR Adams TS Adolfsson J Johansson JE Lowey J Trock BJ Partin AW Walsh PC Trent JM Duggan D Carpten J Chang BL Grönberg H Isaacs WB Xu J 《Nature genetics》2008,40(10):1153-1155
We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, approximately 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 x 10(-9) for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP. 相似文献
15.
Steinthorsdottir V Thorleifsson G Reynisdottir I Benediktsson R Jonsdottir T Walters GB Styrkarsdottir U Gretarsdottir S Emilsson V Ghosh S Baker A Snorradottir S Bjarnason H Ng MC Hansen T Bagger Y Wilensky RL Reilly MP Adeyemo A Chen Y Zhou J Gudnason V Chen G Huang H Lashley K Doumatey A So WY Ma RC Andersen G Borch-Johnsen K Jorgensen T van Vliet-Ostaptchouk JV Hofker MH Wijmenga C Christiansen C Rader DJ Rotimi C Gurney M Chan JC Pedersen O Sigurdsson G Gulcher JR Thorsteinsdottir U Kong A 《Nature genetics》2007,39(6):770-775
16.
Holm H Gudbjartsson DF Sulem P Masson G Helgadottir HT Zanon C Magnusson OT Helgason A Saemundsdottir J Gylfason A Stefansdottir H Gretarsdottir S Matthiasson SE Thorgeirsson GM Jonasdottir A Sigurdsson A Stefansson H Werge T Rafnar T Kiemeney LA Parvez B Muhammad R Roden DM Darbar D Thorleifsson G Walters GB Kong A Thorsteinsdottir U Arnar DO Stefansson K 《Nature genetics》2011,43(4):316-320
Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5 × 10?2?. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant. 相似文献
17.
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes 总被引:1,自引:0,他引:1
Grant SF Thorleifsson G Reynisdottir I Benediktsson R Manolescu A Sainz J Helgason A Stefansson H Emilsson V Helgadottir A Styrkarsdottir U Magnusson KP Walters GB Palsdottir E Jonsdottir T Gudmundsdottir T Gylfason A Saemundsdottir J Wilensky RL Reilly MP Rader DJ Bagger Y Christiansen C Gudnason V Sigurdsson G Thorsteinsdottir U Gulcher JR Kong A Stefansson K 《Nature genetics》2006,38(3):320-323
18.
19.
Study Group of Millennium Genome Project for Cancer Sakamoto H Yoshimura K Saeki N Katai H Shimoda T Matsuno Y Saito D Sugimura H Tanioka F Kato S Matsukura N Matsuda N Nakamura T Hyodo I Nishina T Yasui W Hirose H Hayashi M Toshiro E Ohnami S Sekine A Sato Y Totsuka H Ando M Takemura R Takahashi Y Ohdaira M Aoki K Honmyo I Chiku S Aoyagi K Sasaki H Ohnami S Yanagihara K Yoon KA Kook MC Lee YS Park SR Kim CG Choi IJ Yoshida T Nakamura Y Hirohashi S 《Nature genetics》2008,40(6):730-740
20.
Stacey SN Sulem P Jonasdottir A Masson G Gudmundsson J Gudbjartsson DF Magnusson OT Gudjonsson SA Sigurgeirsson B Thorisdottir K Ragnarsson R Benediktsdottir KR Nexø BA Tjønneland A Overvad K Rudnai P Gurzau E Koppova K Hemminki K Corredera C Fuentelsaz V Grasa P Navarrete S Fuertes F García-Prats MD Sanambrosio E Panadero A De Juan A Garcia A Rivera F Planelles D Soriano V Requena C Aben KK van Rossum MM Cremers RG van Oort IM van Spronsen DJ Schalken JA Peters WH Helfand BT Donovan JL 《Nature genetics》2011,43(11):1098-1103
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27). 相似文献