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Träfflista för sökning "WFRF:(Farrington SM) "

Sökning: WFRF:(Farrington SM)

  • Resultat 1-10 av 18
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1.
  • Jiang, X., et al. (författare)
  • Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
  • 2018
  • Ingår i: Nature Communications. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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2.
  • Tanskanen, T., et al. (författare)
  • Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
  • 2018
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 142:3, s. 540-546
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate<0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.
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3.
  • Thompson, B.A., et al. (författare)
  • Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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  • von Holst, S, et al. (författare)
  • Association studies on 11 published colorectal cancer risk loci
  • 2010
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 103:4, s. 575-580
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort. METHODS: The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype-phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed. RESULTS: Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype-phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age. CONCLUSIONS: Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations.
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10.
  • Ghazi, Sam, et al. (författare)
  • Colorectal cancer susceptibility loci in a population-based study : associations with morphological parameters
  • 2010
  • Ingår i: American Journal of Pathology. - 0002-9440 .- 1525-2191. ; 177:6, s. 2688-2693
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent genome-wide association studies have identified multiple genetic loci and single nucleotide polymorphisms (SNPs) associated with either increased or decreased risk of colorectal cancer (CRC). In the present study, our objective was to determine whether 11 of the new susceptibility CRC loci are associated with tumor morphology and to confirm these loci as distinct and etiologically different risk factors in the development of CRC. The following clinical and morphological parameters were analyzed in 1572 samples: tumor size, T-stage, lymph node metastases, degree of differentiation, mucin production, Crohn-like peritumoral lymphocytic infiltration, tumor-infiltrating lymphocytes, desmoplastic reaction, necrosis, invasion of blood or lymph vessels, perineural growth, medullary type, budding, and tumor margin. One SNP from each of the 11 loci (rs6983267 on 8q24.21, rs16892766 on 8q23.3, rs719725 on 9p24.1, rs10795668 on 10p14, rs3802842 on 11q23.1, rs4444235 on 14q22.2, rs4779584 on 15q13.3, rs9929218 on 16q22.1, rs4939827 on 18q21.1, rs10411210 on 19q13.11, and rs961253 on 20p12.3) was genotyped for all cases. Odds ratios, 95% confidence intervals, and the corresponding P values were calculated for the 11 SNPs identified above. A cross tabulation between SNPs and morphology was performed. Several loci showed statistically significant associations with specific phenotypes. The findings are consistent with pathogenic variants in several loci that act in distinct CRC and morphogenetic pathways. Further large-scale studies are required to validate these findings.
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