Views provided by UsageCounts
Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis
Copyright policy )EC| HYPERGENES ,
NIH| Bioinformatics and Population Genetics to Identify Rheumatoid Arthritis Genes ,
NIH| IDENTIFICATION OF COMMON AND UNCOMMON GENE VARIANTS IN PBC ,
NIH| EPIDEMIOLOGY OF PRIMARY BILIARY CIRRHOSIS
Italian PBC Genetics Study Group; Seldin MF; Gershwin ME; Podda M; de Bakker PI; Cusi D; Siminovitch KA; +63 Authors
Italian PBC Genetics Study Group; Seldin MF; Gershwin ME; Podda M; de Bakker PI; Cusi D; Siminovitch KA; Gregersen PK; Amos CI; Bossa F; Franke A; Shigeta R; Lleo A; Kosoy R; Raychaudhuri S; Ransom M; Invernizzi P; Almasio PL; Alvaro D; Andreone P; Andriulli A; Barlassina C; Benedetti A; Bernuzzi F; Bianchi I; Bragazzi MC; Brunetto M; Bruno S; Caliari L; Casella G; Civardi F; Coco B; Colli A; Colombo M; Colombo S; Cursaro C; Croce LS; Crosignani A; Donato F; Fabris L; Ferrari C; Floreani A; Galli A; Grattagliano I; Lazzari R; Macaluso F; Marra F; Marzioni M; Mattalia A; Montanari R; Morini L; Morisco F; Moroni L; Muratori L; Muratori P; Niro G; Picciotto A; Portincasa P; Prati D; Prisco C; Rosina F; Rossi S; Selmi C; Spinzi G; Strazzabosco M; Tarallo S; Tiribelli C; Toniutto P; Vinci M; Zuin M.;
Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis
Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.
- University of Milan Italy
- The University of Texas System United States
- University of Salford United Kingdom
- University Federico II of Naples Italy
- Brigham and Women's Faulkner Hospital United States
Liver Cirrhosis, 599, genetic risk,, imputation, genetic risk, Gene Frequency, Risk Factors, Genetics (clinical), HLA-DP beta-Chains, antigen-binding pocket; autoimmune disease; genetic risk; imputation; risk allele; Case-Control Studies; European Continental Ancestry Group; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA-DP beta-Chains; HLA-DRB1 Chains; Humans; Italy; Liver Cirrhosis, Biliary; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Risk Factors; Genetics (clinical); Immunology; Genetics, Oligonucleotide Array Sequence Analysis, Liver Cirrhosis, Biliary, Biliary, Single Nucleotide, Cirrhosis, Italy, HLA-DRB1 Chain, Case-Control Studie, antigen-binding pocket,, Human, risk allele,, European Continental Ancestry Group, Immunology, genetic risk,; risk allele,; imputation,; antigen-binding pocket,; Autoimmune Diseases, 610, autoimmune disease, Polymorphism, Single Nucleotide, AUTOIMMUNITY; PRIMARY BILIARY CIRRHOSIS, Article, White People, Autoimmune Diseases, antigen-binding pocket, imputation,, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, antigen-binding pocket; autoimmune disease; genetic risk; imputation; risk allele, genetic risk; risk allele; imputation; antigen-binding pocket; autoimmune disease, risk allele, Oligonucleotide Array Sequence Analysi, Risk Factor, HLA polymorfism, PBC, HLA-DRB1, HLA-DPB1, HLA-DP beta-Chain, Case-Control Studies, Genome-Wide Association Study, HLA-DRB1 Chains
Liver Cirrhosis, 599, genetic risk,, imputation, genetic risk, Gene Frequency, Risk Factors, Genetics (clinical), HLA-DP beta-Chains, antigen-binding pocket; autoimmune disease; genetic risk; imputation; risk allele; Case-Control Studies; European Continental Ancestry Group; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA-DP beta-Chains; HLA-DRB1 Chains; Humans; Italy; Liver Cirrhosis, Biliary; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Risk Factors; Genetics (clinical); Immunology; Genetics, Oligonucleotide Array Sequence Analysis, Liver Cirrhosis, Biliary, Biliary, Single Nucleotide, Cirrhosis, Italy, HLA-DRB1 Chain, Case-Control Studie, antigen-binding pocket,, Human, risk allele,, European Continental Ancestry Group, Immunology, genetic risk,; risk allele,; imputation,; antigen-binding pocket,; Autoimmune Diseases, 610, autoimmune disease, Polymorphism, Single Nucleotide, AUTOIMMUNITY; PRIMARY BILIARY CIRRHOSIS, Article, White People, Autoimmune Diseases, antigen-binding pocket, imputation,, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, antigen-binding pocket; autoimmune disease; genetic risk; imputation; risk allele, genetic risk; risk allele; imputation; antigen-binding pocket; autoimmune disease, risk allele, Oligonucleotide Array Sequence Analysi, Risk Factor, HLA polymorfism, PBC, HLA-DRB1, HLA-DPB1, HLA-DP beta-Chain, Case-Control Studies, Genome-Wide Association Study, HLA-DRB1 Chains
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).77 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10% views 94 - 94views
citations
Citations provided by BIP!
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Citations provided by BIP!popularityPopularity provided by BIP!
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
Popularity provided by BIP!influenceInfluence provided by BIP!
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Influence provided by BIP!impulseImpulse provided by BIP!
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
Impulse provided by BIP!viewsViews provided by UsageCounts
Views provided by UsageCounts 77
Top 10%
Top 10%
Top 10%
94
Green
hybrid