PubMed:23441136
Annnotations
Inflammaging
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 0-149 | Sentence | denotes | Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production. |
| T2 | 150-255 | Sentence | denotes | Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with a strong genetic component. |
| T3 | 256-363 | Sentence | denotes | African-Americans (AA) are at increased risk of SLE, but the genetic basis of this risk is largely unknown. |
| T4 | 364-501 | Sentence | denotes | To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA). |
| T5 | 502-711 | Sentence | denotes | Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22-24 (LOD=6.28), and the admixture signal is associated with the European ancestry (ancestry risk ratio ~1.5). |
| T6 | 712-1139 | Sentence | denotes | Large-scale genotypic analysis on 19,726 individuals of African and European ancestry revealed three independently associated variants in the IFIH1 gene: an intronic variant, rs13023380 [P(meta) = 5.20×10(-14); odds ratio, 95% confidence interval = 0.82 (0.78-0.87)], and two missense variants, rs1990760 (Ala946Thr) [P(meta) = 3.08×10(-7); 0.88 (0.84-0.93)] and rs10930046 (Arg460His) [P(dom) = 1.16×10(-8); 0.70 (0.62-0.79)]. |
| T7 | 1140-1254 | Sentence | denotes | Both missense variants produced dramatic phenotypic changes in apoptosis and inflammation-related gene expression. |
| T8 | 1255-1396 | Sentence | denotes | We experimentally validated function of the intronic SNP by DNA electrophoresis, protein identification, and in vitro protein binding assays. |
| T9 | 1397-1613 | Sentence | denotes | DNA carrying the intronic risk allele rs13023380 showed reduced binding efficiency to a cellular protein complex including nucleolin and lupus autoantigen Ku70/80, and showed reduced transcriptional activity in vivo. |
| T10 | 1614-1777 | Sentence | denotes | Thus, in SLE patients, genetic susceptibility could create a biochemical imbalance that dysregulates nucleolin, Ku70/80, or other nucleic acid regulatory proteins. |
| T11 | 1778-1893 | Sentence | denotes | This could promote antibody hypermutation and auto-antibody generation, further destabilizing the cellular network. |
| T12 | 1894-2114 | Sentence | denotes | Together with molecular modeling, our results establish a distinct role for IFIH1 in apoptosis, inflammation, and autoantibody production, and explain the molecular basis of these three risk alleles for SLE pathogenesis. |
| T1 | 0-149 | Sentence | denotes | Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production. |
| T2 | 150-255 | Sentence | denotes | Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with a strong genetic component. |
| T3 | 256-363 | Sentence | denotes | African-Americans (AA) are at increased risk of SLE, but the genetic basis of this risk is largely unknown. |
| T4 | 364-501 | Sentence | denotes | To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA). |
| T5 | 502-711 | Sentence | denotes | Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22-24 (LOD=6.28), and the admixture signal is associated with the European ancestry (ancestry risk ratio ~1.5). |
| T6 | 712-1139 | Sentence | denotes | Large-scale genotypic analysis on 19,726 individuals of African and European ancestry revealed three independently associated variants in the IFIH1 gene: an intronic variant, rs13023380 [P(meta) = 5.20×10(-14); odds ratio, 95% confidence interval = 0.82 (0.78-0.87)], and two missense variants, rs1990760 (Ala946Thr) [P(meta) = 3.08×10(-7); 0.88 (0.84-0.93)] and rs10930046 (Arg460His) [P(dom) = 1.16×10(-8); 0.70 (0.62-0.79)]. |
| T7 | 1140-1254 | Sentence | denotes | Both missense variants produced dramatic phenotypic changes in apoptosis and inflammation-related gene expression. |
| T8 | 1255-1396 | Sentence | denotes | We experimentally validated function of the intronic SNP by DNA electrophoresis, protein identification, and in vitro protein binding assays. |
| T9 | 1397-1613 | Sentence | denotes | DNA carrying the intronic risk allele rs13023380 showed reduced binding efficiency to a cellular protein complex including nucleolin and lupus autoantigen Ku70/80, and showed reduced transcriptional activity in vivo. |
| T10 | 1614-1777 | Sentence | denotes | Thus, in SLE patients, genetic susceptibility could create a biochemical imbalance that dysregulates nucleolin, Ku70/80, or other nucleic acid regulatory proteins. |
| T11 | 1778-1893 | Sentence | denotes | This could promote antibody hypermutation and auto-antibody generation, further destabilizing the cellular network. |
| T12 | 1894-2114 | Sentence | denotes | Together with molecular modeling, our results establish a distinct role for IFIH1 in apoptosis, inflammation, and autoantibody production, and explain the molecular basis of these three risk alleles for SLE pathogenesis. |
DisGeNET
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T0 | 1970-1975 | gene:64135 | denotes | IFIH1 |
| T1 | 2097-2100 | disease:C0024141 | denotes | SLE |
| R1 | T0 | T1 | associated_with | IFIH1,SLE |
Allie
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| SS1_23441136_1_0 | 150-178 | expanded | denotes | Systemic lupus erythematosus |
| SS2_23441136_1_0 | 180-183 | abbr | denotes | SLE |
| SS1_23441136_2_0 | 256-273 | expanded | denotes | African-Americans |
| SS2_23441136_2_0 | 275-277 | abbr | denotes | AA |
| SS1_23441136_3_0 | 477-495 | expanded | denotes | European-Americans |
| SS2_23441136_3_0 | 497-499 | abbr | denotes | EA |
| AE1_23441136_1_0 | SS1_23441136_1_0 | SS2_23441136_1_0 | abbreviatedTo | Systemic lupus erythematosus,SLE |
| AE1_23441136_2_0 | SS1_23441136_2_0 | SS2_23441136_2_0 | abbreviatedTo | African-Americans,AA |
| AE1_23441136_3_0 | SS1_23441136_3_0 | SS2_23441136_3_0 | abbreviatedTo | European-Americans,EA |
PubmedHPO
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 150-178 | HP_0002725 | denotes | Systemic lupus erythematosus |
| T2 | 204-214 | HP_0002960 | denotes | autoimmune |
| T3 | 204-222 | HP_0002960 | denotes | autoimmune disease |
DisGeNET5_variant_disease
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| 23441136-8#38#48#geners13023380 | 1435-1445 | geners13023380 | denotes | rs13023380 |
| 23441136-8#137#142#diseaseC0024131 | 1534-1539 | diseaseC0024131 | denotes | lupus |
| 23441136-8#137#142#diseaseC0024138 | 1534-1539 | diseaseC0024138 | denotes | lupus |
| 23441136-8#137#142#diseaseC0024141 | 1534-1539 | diseaseC0024141 | denotes | lupus |
| 23441136-8#137#142#diseaseC0409974 | 1534-1539 | diseaseC0409974 | denotes | lupus |
| 38#48#geners13023380137#142#diseaseC0024131 | 23441136-8#38#48#geners13023380 | 23441136-8#137#142#diseaseC0024131 | associated_with | rs13023380,lupus |
| 38#48#geners13023380137#142#diseaseC0024138 | 23441136-8#38#48#geners13023380 | 23441136-8#137#142#diseaseC0024138 | associated_with | rs13023380,lupus |
| 38#48#geners13023380137#142#diseaseC0024141 | 23441136-8#38#48#geners13023380 | 23441136-8#137#142#diseaseC0024141 | associated_with | rs13023380,lupus |
| 38#48#geners13023380137#142#diseaseC0409974 | 23441136-8#38#48#geners13023380 | 23441136-8#137#142#diseaseC0409974 | associated_with | rs13023380,lupus |
DisGeNET5_gene_disease
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| 23441136-0#74#79#gene64135 | 74-79 | gene64135 | denotes | IFIH1 |
| 23441136-0#21#26#diseaseC0024131 | 21-26 | diseaseC0024131 | denotes | lupus |
| 23441136-0#21#26#diseaseC0024138 | 21-26 | diseaseC0024138 | denotes | lupus |
| 23441136-0#21#26#diseaseC0024141 | 21-26 | diseaseC0024141 | denotes | lupus |
| 23441136-0#21#26#diseaseC0409974 | 21-26 | diseaseC0409974 | denotes | lupus |
| 23441136-8#123#132#gene4691 | 1520-1529 | gene4691 | denotes | nucleolin |
| 23441136-8#155#159#gene2547 | 1552-1556 | gene2547 | denotes | Ku70 |
| 23441136-8#137#142#diseaseC0024131 | 1534-1539 | diseaseC0024131 | denotes | lupus |
| 23441136-8#137#142#diseaseC0024138 | 1534-1539 | diseaseC0024138 | denotes | lupus |
| 23441136-8#137#142#diseaseC0024141 | 1534-1539 | diseaseC0024141 | denotes | lupus |
| 23441136-8#137#142#diseaseC0409974 | 1534-1539 | diseaseC0409974 | denotes | lupus |
| 23441136-8#137#142#diseaseC0024131 | 1534-1539 | diseaseC0024131 | denotes | lupus |
| 23441136-8#137#142#diseaseC0024138 | 1534-1539 | diseaseC0024138 | denotes | lupus |
| 23441136-8#137#142#diseaseC0024141 | 1534-1539 | diseaseC0024141 | denotes | lupus |
| 23441136-8#137#142#diseaseC0409974 | 1534-1539 | diseaseC0409974 | denotes | lupus |
| 74#79#gene6413521#26#diseaseC0024131 | 23441136-0#74#79#gene64135 | 23441136-0#21#26#diseaseC0024131 | associated_with | IFIH1,lupus |
| 74#79#gene6413521#26#diseaseC0024138 | 23441136-0#74#79#gene64135 | 23441136-0#21#26#diseaseC0024138 | associated_with | IFIH1,lupus |
| 74#79#gene6413521#26#diseaseC0024141 | 23441136-0#74#79#gene64135 | 23441136-0#21#26#diseaseC0024141 | associated_with | IFIH1,lupus |
| 74#79#gene6413521#26#diseaseC0409974 | 23441136-0#74#79#gene64135 | 23441136-0#21#26#diseaseC0409974 | associated_with | IFIH1,lupus |
| 123#132#gene4691137#142#diseaseC0024131 | 23441136-8#123#132#gene4691 | 23441136-8#137#142#diseaseC0024131 | associated_with | nucleolin,lupus |
| 123#132#gene4691137#142#diseaseC0024138 | 23441136-8#123#132#gene4691 | 23441136-8#137#142#diseaseC0024138 | associated_with | nucleolin,lupus |
| 123#132#gene4691137#142#diseaseC0024141 | 23441136-8#123#132#gene4691 | 23441136-8#137#142#diseaseC0024141 | associated_with | nucleolin,lupus |
| 123#132#gene4691137#142#diseaseC0409974 | 23441136-8#123#132#gene4691 | 23441136-8#137#142#diseaseC0409974 | associated_with | nucleolin,lupus |
| 123#132#gene4691137#142#diseaseC0024131 | 23441136-8#123#132#gene4691 | 23441136-8#137#142#diseaseC0024131 | associated_with | nucleolin,lupus |
| 123#132#gene4691137#142#diseaseC0024138 | 23441136-8#123#132#gene4691 | 23441136-8#137#142#diseaseC0024138 | associated_with | nucleolin,lupus |
| 123#132#gene4691137#142#diseaseC0024141 | 23441136-8#123#132#gene4691 | 23441136-8#137#142#diseaseC0024141 | associated_with | nucleolin,lupus |
| 123#132#gene4691137#142#diseaseC0409974 | 23441136-8#123#132#gene4691 | 23441136-8#137#142#diseaseC0409974 | associated_with | nucleolin,lupus |
| 155#159#gene2547137#142#diseaseC0024131 | 23441136-8#155#159#gene2547 | 23441136-8#137#142#diseaseC0024131 | associated_with | Ku70,lupus |
| 155#159#gene2547137#142#diseaseC0024138 | 23441136-8#155#159#gene2547 | 23441136-8#137#142#diseaseC0024138 | associated_with | Ku70,lupus |
| 155#159#gene2547137#142#diseaseC0024141 | 23441136-8#155#159#gene2547 | 23441136-8#137#142#diseaseC0024141 | associated_with | Ku70,lupus |
| 155#159#gene2547137#142#diseaseC0409974 | 23441136-8#155#159#gene2547 | 23441136-8#137#142#diseaseC0409974 | associated_with | Ku70,lupus |
| 155#159#gene2547137#142#diseaseC0024131 | 23441136-8#155#159#gene2547 | 23441136-8#137#142#diseaseC0024131 | associated_with | Ku70,lupus |
| 155#159#gene2547137#142#diseaseC0024138 | 23441136-8#155#159#gene2547 | 23441136-8#137#142#diseaseC0024138 | associated_with | Ku70,lupus |
| 155#159#gene2547137#142#diseaseC0024141 | 23441136-8#155#159#gene2547 | 23441136-8#137#142#diseaseC0024141 | associated_with | Ku70,lupus |
| 155#159#gene2547137#142#diseaseC0409974 | 23441136-8#155#159#gene2547 | 23441136-8#137#142#diseaseC0409974 | associated_with | Ku70,lupus |