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Amundadottir LT Sulem P Gudmundsson J Helgason A Baker A Agnarsson BA Sigurdsson A Benediktsdottir KR Cazier JB Sainz J Jakobsdottir M Kostic J Magnusdottir DN Ghosh S Agnarsson K Birgisdottir B Le Roux L Olafsdottir A Blondal T Andresdottir M Gretarsdottir OS Bergthorsson JT Gudbjartsson D Gylfason A Thorleifsson G Manolescu A Kristjansson K Geirsson G Isaksson H Douglas J Johansson JE Bälter K Wiklund F Montie JE Yu X Suarez BK Ober C Cooney KA Gronberg H Catalona WJ Einarsson GV 《Nature genetics》2006,38(6):652-658
With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry. 相似文献
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Stefansson H Helgason A Thorleifsson G Steinthorsdottir V Masson G Barnard J Baker A Jonasdottir A Ingason A Gudnadottir VG Desnica N Hicks A Gylfason A Gudbjartsson DF Jonsdottir GM Sainz J Agnarsson K Birgisdottir B Ghosh S Olafsdottir A Cazier JB Kristjansson K Frigge ML Thorgeirsson TE Gulcher JR Kong A Stefansson K 《Nature genetics》2005,37(2):129-137
A refined physical map of chromosome 17q21.31 uncovered a 900-kb inversion polymorphism. Chromosomes with the inverted segment in different orientations represent two distinct lineages, H1 and H2, that have diverged for as much as 3 million years and show no evidence of having recombined. The H2 lineage is rare in Africans, almost absent in East Asians but found at a frequency of 20% in Europeans, in whom the haplotype structure is indicative of a history of positive selection. Here we show that the H2 lineage is undergoing positive selection in the Icelandic population, such that carrier females have more children and have higher recombination rates than noncarriers. 相似文献
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The highly invasive New Zealand mudsnail, Potamopyrgus antipodarum , may compete with and displace native North American macroinvertebrates in freshwater systems wherever it becomes established. Densities and spatial distributions of 3 snail species including P. antipodarum and the threatened Taylorconcha serpenticola were compared among 3 adjacent habitat types (run, edge, and vegetation) in Banbury Springs, a tributary of the Snake River, near Hagerman, Idaho, USA. In all 3 habitats P. antipodarum was the most abundant snail species. All 3 species densities were highly variable within habitats, suggesting a nonrandom distribution pattern. Densities of P. antipodarum were significantly greatest in the vegetation habitat type, while densities of T. serpenticola were similar among habitats. Smallersized P. antipodarum were less abundant in the run habitat with its associated higher water velocities, and their densities were negatively correlated with velocity. Densities of P. antipodarum also were negatively correlated with distance from the highly infested, man-made Morgan Lake, while T. serpenticola densities were positively correlated with distance from Morgan Lake. Potamopyrgus antipodarum is a potential competitor with native aquatic species, although its colonization into some freshwater habitats may be limited. 相似文献
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Jaeger E Webb E Howarth K Carvajal-Carmona L Rowan A Broderick P Walther A Spain S Pittman A Kemp Z Sullivan K Heinimann K Lubbe S Domingo E Barclay E Martin L Gorman M Chandler I Vijayakrishnan J Wood W Papaemmanuil E Penegar S Qureshi M;CORGI Consortium Farrington S Tenesa A Cazier JB Kerr D Gray R Peto J Dunlop M Campbell H Thomas H Houlston R Tomlinson I 《Nature genetics》2008,40(1):26-28
We mapped a high-penetrance gene (CRAC1; also known as HMPS) associated with colorectal cancer (CRC) in the Ashkenazi population to a 0.6-Mb region on chromosome 15 containing SCG5 (also known as SGNE1), GREM1 and FMN1. We hypothesized that the CRAC1 locus harbored low-penetrance variants that increased CRC risk in the general population. In a large series of colorectal cancer cases and controls, SNPs near GREM1 and SCG5 were strongly associated with increased CRC risk (for rs4779584, P = 4.44 x 10(-14)). 相似文献
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Broderick P Carvajal-Carmona L Pittman AM Webb E Howarth K Rowan A Lubbe S Spain S Sullivan K Fielding S Jaeger E Vijayakrishnan J Kemp Z Gorman M Chandler I Papaemmanuil E Penegar S Wood W Sellick G Qureshi M Teixeira A Domingo E Barclay E Martin L Sieber O;CORGI Consortium Kerr D Gray R Peto J Cazier JB Tomlinson I Houlston RS 《Nature genetics》2007,39(11):1315-1317
To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 individuals with familial colorectal tumor (627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication sample sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF-beta and Wnt signaling) associated with CRC. Across the four sample sets, the association between rs4939827 and CRC was highly statistically significant (P(trend) = 1.0 x 10(-12)). 相似文献
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A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21 总被引:16,自引:0,他引:16
Tomlinson I Webb E Carvajal-Carmona L Broderick P Kemp Z Spain S Penegar S Chandler I Gorman M Wood W Barclay E Lubbe S Martin L Sellick G Jaeger E Hubner R Wild R Rowan A Fielding S Howarth K;CORGI Consortium Silver A Atkin W Muir K Logan R Kerr D Johnstone E Sieber O Gray R Thomas H Peto J Cazier JB Houlston R 《Nature genetics》2007,39(8):984-988
Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 x 10(-7), allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 x 10(-14) (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34; P = 6.89 x 10(-5)). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia. 相似文献
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Dunlop MG Dobbins SE Farrington SM Jones AM Palles C Whiffin N Tenesa A Spain S Broderick P Ooi LY Domingo E Smillie C Henrion M Frampton M Martin L Grimes G Gorman M Semple C Ma YP Barclay E Prendergast J Cazier JB Olver B Penegar S Lubbe S Chander I Carvajal-Carmona LG Ballereau S Lloyd A Vijayakrishnan J Zgaga L Rudan I Theodoratou E;Colorectal Tumour Gene Identification 《Nature genetics》2012,44(7):770-776
We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC. 相似文献
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