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- Law, PJ, et al.
(författare)
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Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 14175-
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Tidskriftsartikel (refereegranskat)abstract
- Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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- Margaritte-Jeannin, P, et al.
(författare)
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HLA-DQ relative risks for coeliac disease in European populations: a study of the European Genetics Cluster on Coeliac Disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 63:6, s. 562-7
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Tidskriftsartikel (refereegranskat)abstract
- Coeliac disease is an enteropathy due to an intolerance to gluten. The association between HLA-DQ genes and CD is well established. The majority of patients carry the HLA-DQ heterodimer encoded by DQA1*05/DQB1*02, either in cis or in trans. The remaining patients carry either part of the DQ heterodimer or DQA1*03-DQB1*0302. The aim of the study was to estimate the risks associated with different DQ genotypes in European populations. HLA information was available for 470 trio families from four countries: France (117), Italy (128), and Norway and Sweden (225). Five DQA1-DQB1 haplotypes were considered and control haplotype frequencies were estimated from the set of parental haplotypes not transmitted to the affected child. The possible genotypes were grouped into five genotype groups, based on the hierarchy of risk reported in the literature. A north-south gradient in the genotype group frequencies is observed in probands: homogeneity is strongly rejected between all country pairs. For each country, the relative risks associated with each genotype group were computed taking into account the control haplotype frequencies. Homogeneity of relative risks between countries was tested pairwise by maximum likelihood ratio statistics. The hypothesis of homogeneity of relative risks is rejected (P is approximately 10(-6)) for all country pairs. In conclusion, the gradient in the genotype group frequencies in probands is not only due to differences in haplotype frequencies but also due to differences in genotype relative risks in the studied populations; the relative risks associated with each DQ genotype group are different between northern and southern European countries; neither are they ordered in the same way.
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- Holopainen, Päivi, et al.
(författare)
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Candidate gene region 2q33 in European families with coeliac disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 63:3, s. 212-22
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome region 2q33 harbours a cluster of genes, CTLA-4, CD28, ICOS and closely located PD-1, all related to immune activation and considered as promising candidate genes for susceptibility to coeliac disease (CD). We present here the results of a genetic linkage and association analysis of nine markers located in this gene region in a large combined European material of 796 families with CD from Finland, Sweden, Norway, UK, France and Italy. The joint analysis supports earlier findings that this susceptibility locus, assigned as CELIAC3, merits further studies. Nominally significant linkage to CD was found in 314 families including affected sib pairs. Each of the five populations showed weak associations to several marker alleles, but the analysis revealed, however, no conclusive evidence for a primary functional gene or gene variant present in the total set of families. The results suggest that the CD risk due to 2q33 gene region is complex and may involve more than one susceptibility allele, which possibly differ from other autoimmune diseases.
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