14 results on '"Williams, Adrienne H."'
Search Results
2. sj-pdf-5-obm-10.1177_1753495X221133150 - Supplemental material for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease
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Bleyer, Anthony J, Kidd, Kendrah O, Williams, Adrienne H, Johnson, Emily, Robins, Victoria, Martin, Lauren, Taylor, Abbigail, Kim, Alice, Bowline, Isai, Connaughton, Dervla M, Langefeld, Carl D, Zivna, Martina, and Kmoch, Stanislav
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FOS: Clinical medicine ,111402 Obstetrics and Gynaecology - Abstract
Supplemental material, sj-pdf-5-obm-10.1177_1753495X221133150 for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease by Anthony J Bleyer, Kendrah O Kidd, Adrienne H Williams, Emily Johnson, Victoria Robins, Lauren Martin, Abbigail Taylor, Alice Kim, Isai Bowline, Dervla M Connaughton, Carl D Langefeld, Martina Zivna and Stanislav Kmoch in Obstetric Medicine
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- 2022
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3. sj-docx-1-obm-10.1177_1753495X221133150 - Supplemental material for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease
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Bleyer, Anthony J, Kidd, Kendrah O, Williams, Adrienne H, Johnson, Emily, Robins, Victoria, Martin, Lauren, Taylor, Abbigail, Kim, Alice, Bowline, Isai, Connaughton, Dervla M, Langefeld, Carl D, Zivna, Martina, and Kmoch, Stanislav
- Subjects
FOS: Clinical medicine ,111402 Obstetrics and Gynaecology - Abstract
Supplemental material, sj-docx-1-obm-10.1177_1753495X221133150 for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease by Anthony J Bleyer, Kendrah O Kidd, Adrienne H Williams, Emily Johnson, Victoria Robins, Lauren Martin, Abbigail Taylor, Alice Kim, Isai Bowline, Dervla M Connaughton, Carl D Langefeld, Martina Zivna and Stanislav Kmoch in Obstetric Medicine
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- 2022
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4. sj-pptx-2-obm-10.1177_1753495X221133150 - Supplemental material for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease
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Bleyer, Anthony J, Kidd, Kendrah O, Williams, Adrienne H, Johnson, Emily, Robins, Victoria, Martin, Lauren, Taylor, Abbigail, Kim, Alice, Bowline, Isai, Connaughton, Dervla M, Langefeld, Carl D, Zivna, Martina, and Kmoch, Stanislav
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FOS: Clinical medicine ,111402 Obstetrics and Gynaecology - Abstract
Supplemental material, sj-pptx-2-obm-10.1177_1753495X221133150 for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease by Anthony J Bleyer, Kendrah O Kidd, Adrienne H Williams, Emily Johnson, Victoria Robins, Lauren Martin, Abbigail Taylor, Alice Kim, Isai Bowline, Dervla M Connaughton, Carl D Langefeld, Martina Zivna and Stanislav Kmoch in Obstetric Medicine
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- 2022
- Full Text
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5. sj-pdf-4-obm-10.1177_1753495X221133150 - Supplemental material for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease
- Author
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Bleyer, Anthony J, Kidd, Kendrah O, Williams, Adrienne H, Johnson, Emily, Robins, Victoria, Martin, Lauren, Taylor, Abbigail, Kim, Alice, Bowline, Isai, Connaughton, Dervla M, Langefeld, Carl D, Zivna, Martina, and Kmoch, Stanislav
- Subjects
FOS: Clinical medicine ,111402 Obstetrics and Gynaecology - Abstract
Supplemental material, sj-pdf-4-obm-10.1177_1753495X221133150 for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease by Anthony J Bleyer, Kendrah O Kidd, Adrienne H Williams, Emily Johnson, Victoria Robins, Lauren Martin, Abbigail Taylor, Alice Kim, Isai Bowline, Dervla M Connaughton, Carl D Langefeld, Martina Zivna and Stanislav Kmoch in Obstetric Medicine
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- 2022
- Full Text
- View/download PDF
6. sj-pdf-5-obm-10.1177_1753495X221133150 - Supplemental material for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease
- Author
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Bleyer, Anthony J, Kidd, Kendrah O, Williams, Adrienne H, Johnson, Emily, Robins, Victoria, Martin, Lauren, Taylor, Abbigail, Kim, Alice, Bowline, Isai, Connaughton, Dervla M, Langefeld, Carl D, Zivna, Martina, and Kmoch, Stanislav
- Subjects
FOS: Clinical medicine ,111402 Obstetrics and Gynaecology - Abstract
Supplemental material, sj-pdf-5-obm-10.1177_1753495X221133150 for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease by Anthony J Bleyer, Kendrah O Kidd, Adrienne H Williams, Emily Johnson, Victoria Robins, Lauren Martin, Abbigail Taylor, Alice Kim, Isai Bowline, Dervla M Connaughton, Carl D Langefeld, Martina Zivna and Stanislav Kmoch in Obstetric Medicine
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- 2022
- Full Text
- View/download PDF
7. sj-docx-1-obm-10.1177_1753495X221133150 - Supplemental material for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease
- Author
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Bleyer, Anthony J, Kidd, Kendrah O, Williams, Adrienne H, Johnson, Emily, Robins, Victoria, Martin, Lauren, Taylor, Abbigail, Kim, Alice, Bowline, Isai, Connaughton, Dervla M, Langefeld, Carl D, Zivna, Martina, and Kmoch, Stanislav
- Subjects
FOS: Clinical medicine ,111402 Obstetrics and Gynaecology - Abstract
Supplemental material, sj-docx-1-obm-10.1177_1753495X221133150 for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease by Anthony J Bleyer, Kendrah O Kidd, Adrienne H Williams, Emily Johnson, Victoria Robins, Lauren Martin, Abbigail Taylor, Alice Kim, Isai Bowline, Dervla M Connaughton, Carl D Langefeld, Martina Zivna and Stanislav Kmoch in Obstetric Medicine
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- 2022
- Full Text
- View/download PDF
8. sj-pdf-3-obm-10.1177_1753495X221133150 - Supplemental material for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease
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Bleyer, Anthony J, Kidd, Kendrah O, Williams, Adrienne H, Johnson, Emily, Robins, Victoria, Martin, Lauren, Taylor, Abbigail, Kim, Alice, Bowline, Isai, Connaughton, Dervla M, Langefeld, Carl D, Zivna, Martina, and Kmoch, Stanislav
- Subjects
FOS: Clinical medicine ,111402 Obstetrics and Gynaecology - Abstract
Supplemental material, sj-pdf-3-obm-10.1177_1753495X221133150 for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease by Anthony J Bleyer, Kendrah O Kidd, Adrienne H Williams, Emily Johnson, Victoria Robins, Lauren Martin, Abbigail Taylor, Alice Kim, Isai Bowline, Dervla M Connaughton, Carl D Langefeld, Martina Zivna and Stanislav Kmoch in Obstetric Medicine
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- 2022
- Full Text
- View/download PDF
9. sj-pdf-3-obm-10.1177_1753495X221133150 - Supplemental material for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease
- Author
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Bleyer, Anthony J, Kidd, Kendrah O, Williams, Adrienne H, Johnson, Emily, Robins, Victoria, Martin, Lauren, Taylor, Abbigail, Kim, Alice, Bowline, Isai, Connaughton, Dervla M, Langefeld, Carl D, Zivna, Martina, and Kmoch, Stanislav
- Subjects
FOS: Clinical medicine ,111402 Obstetrics and Gynaecology - Abstract
Supplemental material, sj-pdf-3-obm-10.1177_1753495X221133150 for Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease by Anthony J Bleyer, Kendrah O Kidd, Adrienne H Williams, Emily Johnson, Victoria Robins, Lauren Martin, Abbigail Taylor, Alice Kim, Isai Bowline, Dervla M Connaughton, Carl D Langefeld, Martina Zivna and Stanislav Kmoch in Obstetric Medicine
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- 2022
- Full Text
- View/download PDF
10. Genome-Wide Association Study Identifies Loci for Liver Enzyme Concentrations in Mexican Americans: The GUARDIAN Consortium
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Young, Kendra A, Palmer, Nicholette D, Fingerlin, Tasha E, Langefeld, Carl D, Norris, Jill M, Wang, Nan, Xiang, Anny H, Guo, Xiuqing, Williams, Adrienne H, Chen, Yii-Der I, Taylor, Kent D, Rotter, Jerome I, Raffel, Leslie J, Goodarzi, Mark O, Watanabe, Richard M, and Wagenknecht, Lynne E
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Adult ,Male ,Chronic Liver Disease and Cirrhosis ,digestive system ,Endocrinology & Metabolism ,Clinical Research ,Non-alcoholic Fatty Liver Disease ,Mexican Americans ,Genetics ,Humans ,Aspartate Aminotransferases ,Polymorphism ,Prevention ,Liver Disease ,Human Genome ,Membrane Proteins ,Alanine Transaminase ,Lipase ,gamma-Glutamyltransferase ,Single Nucleotide ,Middle Aged ,digestive system diseases ,Liver ,Genetic Loci ,Linear Models ,Female ,Digestive Diseases ,Genome-Wide Association Study - Abstract
ObjectivePopulations of Mexican American ancestry are at an increased risk for nonalcoholic fatty liver disease. The objective of this study was to determine whether loci in known and novel genes were associated with variation in aspartate aminotransferase (AST) (n = 3,644), alanine aminotransferase (ALT) (n = 3,595), and gamma-glutamyl transferase (GGT) (n = 1,577) levels by conducting the first genome-wide association study (GWAS) of liver enzymes, which commonly measure liver function, in individuals of Mexican American ancestry.MethodsLevels of AST, ALT, and GGT were determined by enzymatic colorimetric assays. A multi-cohort GWAS of individuals of Mexican American ancestry was performed. Single-nucleotide polymorphisms (SNP) were tested for association with liver outcomes by multivariable linear regression using an additive genetic model. Association analyses were conducted separately in each cohort, followed by a nonparametric meta-analysis.ResultsIn the PNPLA3 gene, rs4823173 (P = 3.44 × 10-10 ), rs2896019 (P = 7.29 × 10-9 ), and rs2281135 (P = 8.73 × 10-9 ) were significantly associated with AST levels. Although not genome-wide significant, these same SNPs were the top hits for ALT (P = 7.12 × 10-8 , P = 1.98 × 10-7 , and P = 1.81 × 10-7 , respectively). The strong correlation (r2 = 1.0) for these SNPs indicated a single hit in the PNPLA3 gene. No genome-wide significant associations were found for GGT.ConclusionsPNPLA3, a locus previously identified with ALT, AST, and nonalcoholic fatty liver disease in European and Japanese GWAS, is also associated with liver enzymes in populations of Mexican American ancestry.
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- 2019
11. Evaluation ofTRAF6in a large multiancestral lupus cohort
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Namjou, Bahram, Choi, Chan-Bum, Harley, Isaac T. W., Alarcón-Riquelme, Marta E., Kelly, Jennifer A., Glenn, Stuart B., Ojwang, Joshua O., Adler, Adam, Kwangwoo Kim, Gallant, Caroline J., Boackle, Susan A., Criswell, Lindsey A., Kimberly, Robert P., Brown, Elizabeth E., Edberg, Jeffrey, Alarcón, Graciela S., Stevens, Anne M., Jacob, Chaim O., Gilkeson, Gary S., Kamen, Diane L., Tsao, Betty P., Anaya, Juan-Manuel, Kim, Eun-Mi, Park, So-Yeon, Sung, Yoon-Kyoung, Guthridge, Joel M., Merrill, Joan T., Petri, Michelle, Ramsey-Goldman, Rosalind, Vilá, Luis M., Niewold, Timothy B., Martin, Javier, Pons-Estel, Bernardo A., Vyse, Timothy J., Freedman, Barry I., Moser, Kathy L., Gaffney, Patrick M., Williams, Adrienne H., Comeau, Mary E., Reveille, John D., Kang, Changwon, James, Judith A., Scofield, R. Hal, Langefeld, Carl D., Kaufman, Kenneth M., Harley, John B., Bae, Sang-Cheol, Junker, Peter, Voss, Anne, and Laustrup, Helle
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single nucleotide ,Male ,Linkage disequilibrium ,Candidate gene ,Heredity ,Organogenesis ,Tumor necrosis factor receptor associated factor 6 ,Genome-wide association study ,Signal transduction ,Cohort Studies ,Genetic heterogeneity ,Gene Frequency ,immune system diseases ,Ethnicity ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Pharmacology (medical) ,skin and connective tissue diseases ,Priority journal ,education.field_of_study ,Calculation ,Gene linkage disequilibrium ,Female ,Human ,Immunopathogenesis ,Genotype ,Immunology ,Population ,Single-nucleotide polymorphism ,Major clinical study ,Biology ,Pedigree analysis ,Polymorphism, Single Nucleotide ,Article ,Systemic lupus erythematosus ,Rheumatology ,Population based case control study ,Humans ,Genetic Predisposition to Disease ,African american ,Rheumatoid arthritis ,Polymorphism ,education ,Alleles ,Genetic Association Studies ,Genetic association ,TNF Receptor-Associated Factor 6 ,Lupus erythematosus ,Immunity ,Case-control study ,Odds ratio ,systemic ,Thrombocytopenia ,Single nucleotide polymorphism ,Haplotypes ,Case-Control Studies ,Meta analysis (topic) ,Controlled study - Abstract
Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development. Methods Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10 -5 and P = 4.73 × 10 -5, respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r 2 = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10 -4, OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10 -6, OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model. Conclusion Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity. Copyright © 2012 by the American College of Rheumatology.
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- 2012
12. End-stage renal disease in African Americans with lupus nephritis is associated with APOL1
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Freedman, Barry I, Langefeld, Carl D, Andringa, Kelly K, Croker, Jennifer A, Williams, Adrienne H, Garner, Neva E, Birmingham, Daniel J, Hebert, Lee A, Hicks, Pamela J, Segal, Mark S, Edberg, Jeffrey C, Brown, Elizabeth E, Alarcón, Graciela S, Costenbader, Karen H, Comeau, Mary E, Criswell, Lindsey A, Harley, John B, James, Judith A, Kamen, Diane L, Lim, S Sam, Merrill, Joan T, Sivils, Kathy L, Niewold, Timothy B, Patel, Neha M, Petri, Michelle, Ramsey-Goldman, Rosalind, Reveille, John D, Salmon, Jane E, Tsao, Betty P, Gibson, Keisha L, Byers, Joyce R, Vinnikova, Anna K, Lea, Janice P, Julian, Bruce A, Kimberly, Robert P, and Lupus Nephritis–End‐Stage Renal Disease Consortium
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Adult ,Male ,Kidney Disease ,HDL ,Genotype ,Lipoproteins ,Clinical Sciences ,Immunology ,Lupus ,Autoimmune Disease ,White People ,Kidney Failure ,Risk Factors ,Clinical Research ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Genetic Testing ,Chronic ,Aetiology ,Alleles ,Lupus Nephritis–End‐Stage Renal Disease Consortium ,Inflammatory and immune system ,Middle Aged ,Apolipoprotein L1 ,Lupus Nephritis ,Arthritis & Rheumatology ,Black or African American ,Apolipoproteins ,Logistic Models ,Disease Progression ,Public Health and Health Services ,Female - Abstract
ObjectiveLupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that exhibits familial aggregation and may progress to end-stage renal disease (ESRD). LN is more prevalent among African Americans than among European Americans. This study was undertaken to investigate the hypothesis that the apolipoprotein L1 gene (APOL1) nephropathy risk alleles G1/G2, common in African Americans and rare in European Americans, contribute to the ethnic disparity in risk.MethodsAPOL1 G1 and G2 nephropathy alleles were genotyped in 855 African American SLE patients with LN-ESRD (cases) and 534 African American SLE patients without nephropathy (controls) and tested for association under a recessive genetic model, by logistic regression.ResultsNinety percent of the SLE patients were female. The mean ± SD age at SLE diagnosis was significantly lower in LN-ESRD cases than in SLE non-nephropathy controls (27.3 ± 10.9 years versus 39.5 ± 12.2 years). The mean ± SD time from SLE diagnosis to development of LN-ESRD in cases was 7.3 ± 7.2 years. The G1/G2 risk alleles were strongly associated with SLE-ESRD, with 25% of cases and 12% of controls having 2 nephropathy alleles (odds ratio [OR] 2.57, recessive model P = 1.49 × 10(-9)), and after adjustment for age, sex, and ancestry admixture (OR 2.72, P = 6.23 × 10(-6)). The age-, sex-, and admixture-adjusted population attributable risk for ESRD among patients with G1/G2 polymorphisms was 0.26, compared to 0.003 among European American patients. The mean time from SLE diagnosis to ESRD development was ∼2 years earlier among individuals with APOL1 risk genotypes (P = 0.01).ConclusionAPOL1 G1/G2 alleles strongly impact the risk of LN-ESRD in African Americans, as well as the time to progression to ESRD. The high frequency of these alleles in African Americans with near absence in European Americans explains an important proportion of the increased risk of LN-ESRD in African Americans.
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- 2014
13. Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups
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Kaufman, Kenneth M, Zhao, Jian, Kelly, Jennifer A, Hughes, Travis, Adler, Adam, Sanchez, Elena, Ojwang, Joshua O, Langefeld, Carl D, Ziegler, Julie T, Williams, Adrienne H, Comeau, Mary E, Marion, Miranda C, Glenn, Stuart B, Cantor, Rita M, Grossman, Jennifer M, Hahn, Bevra H, Song, Yeong Wook, Yu, Chack-Yung, James, Judith A, Guthridge, Joel M, Brown, Elizabeth E, Alarcón, Graciela S, Kimberly, Robert P, Edberg, Jeffrey C, Ramsey-Goldman, Rosalind, Petri, Michelle A, Reveille, John D, Vilá, Luis M, Anaya, Juan-Manuel, Boackle, Susan A, Stevens, Anne M, Freedman, Barry I, Criswell, Lindsey A, Pons Estel, Bernardo A, Argentine Collaborative Group, Lee, Joo-Hyun, Lee, Ji-Seon, Chang, Deh-Ming, Scofield, R Hal A, Gilkeson, Gary S, Merrill, Joan T, Niewold, Timothy B, Vyse, Timothy James, Bae, Sang-Cheol, Alarcón-Riquelme, Marta E, BIOLUPUS network, Jacob, Chaim O, Moser Sivils, Kathy, Gaffney, Patrick M, Harley, John B, Sawalha, Amr H, and Tsao, Betty P
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Genotype ,Methyl-CpG-Binding Protein 2 ,Molecular Sequence Data ,Clinical Sciences ,Immunology ,Lupus ,Real-Time Polymerase Chain Reaction ,Autoimmune Disease ,Chromosomes ,BIOLUPUS network ,Risk Factors ,Clinical Research ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Polymorphism ,Aetiology ,Lupus Erythematosus ,Base Sequence ,Inflammatory and immune system ,Systemic ,Racial Groups ,Human Genome ,Argentine Collaborative Group ,Chromosome Mapping ,Single Nucleotide ,Arthritis & Rheumatology ,Interleukin-1 Receptor-Associated Kinases ,Haplotypes ,Public Health and Health Services ,Human - Abstract
ObjectivesThe Xq28 region containing IRAK1 and MECP2 has been identified as a risk locus for systemic lupus erythematosus (SLE) in previous genetic association studies. However, due to the strong linkage disequilibrium between IRAK1 and MECP2, it remains unclear which gene is affected by the underlying causal variant(s) conferring risk of SLE.MethodsWe fine-mapped ≥136 SNPs in a ∼227 kb region on Xq28, containing IRAK1, MECP2 and seven adjacent genes (L1CAM, AVPR2, ARHGAP4, NAA10, RENBP, HCFC1 and TMEM187), for association with SLE in 15 783 case-control subjects derived from four different ancestral groups.ResultsMultiple SNPs showed strong association with SLE in European Americans, Asians and Hispanics at p
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- 2013
14. Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus
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Adrianto, Indra, Wang, Shaofeng, Wiley, Graham B, Lessard, Christopher J, Kelly, Jennifer A, Adler, Adam J, Glenn, Stuart B, Williams, Adrienne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, Wakeland, Benjamin E, Liang, Chaoying, Kaufman, Kenneth M, Guthridge, Joel M, Alarcón-Riquelme, Marta E, BIOLUPUS and GENLES Networks, Alarcón, Graciela S, Anaya, Juan-Manuel, Bae, Sang-Cheol, Kim, Jae-Hoon, Joo, Young Bin, Boackle, Susan A, Brown, Elizabeth E, Petri, Michelle A, Ramsey-Goldman, Rosalind, Reveille, John D, Vilá, Luis M, Criswell, Lindsey A, Edberg, Jeffrey C, Freedman, Barry I, Gilkeson, Gary S, Jacob, Chaim O, James, Judith A, Kamen, Diane L, Kimberly, Robert P, Martín, Javier, Merrill, Joan T, Niewold, Timothy B, Pons-Estel, Bernardo A, Scofield, R Hal, Stevens, Anne M, Tsao, Betty P, Vyse, Timothy J, Langefeld, Carl D, Harley, John B, Wakeland, Edward K, Moser, Kathy L, Montgomery, Courtney G, and Gaffney, Patrick M
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Genetic Markers ,Male ,Clinical Sciences ,Immunology ,Lupus ,Autoimmune Disease ,White People ,Cell Line ,Risk Factors ,Clinical Research ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Polymorphism ,Aetiology ,B-Lymphocytes ,BIOLUPUS and GENLES Networks ,Lupus Erythematosus ,Asian ,Inflammatory and immune system ,Systemic ,Human Genome ,Intracellular Signaling Peptides and Proteins ,Signal Transducing ,Adaptor Proteins ,Single Nucleotide ,Hispanic or Latino ,United States ,Neoplasm Proteins ,Arthritis & Rheumatology ,DNA-Binding Proteins ,Black or African American ,Transformed ,Haplotypes ,Public Health and Health Services ,Female - Abstract
ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome-wide association studies have identified >30 SLE susceptibility genes. One of these genes, TNIP1, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting NF-κB signaling. The present study was undertaken to investigate the genetic factors that influence association with SLE in genes that regulate the NF-κB pathway.MethodsWe analyzed a dense set of genetic markers spanning TNIP1 and TAX1BP1, as well as the TNIP1 homolog TNIP2, in case-control populations of diverse ethnic origins. TNIP1, TNIP2, and TAX1BP1 were fine-mapped in a total of 8,372 SLE cases and 7,492 healthy controls from European-ancestry, African American, Hispanic, East Asian, and African American Gullah populations. Levels of TNIP1 messenger RNA (mRNA) and ABIN1 protein in Epstein-Barr virus-transformed human B cell lines were analyzed by quantitative reverse transcription-polymerase chain reaction and Western blotting, respectively.ResultsWe found significant associations between SLE and genetic variants within TNIP1, but not in TNIP2 or TAX1BP1. After resequencing and imputation, we identified 2 independent risk haplotypes within TNIP1 in individuals of European ancestry that were also present in African American and Hispanic populations. Levels of TNIP1 mRNA and ABIN1 protein were reduced among subjects with these haplotypes, suggesting that they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression.ConclusionOur results confirm the association signals between SLE and TNIP1 variants in multiple populations and provide new insight into the mechanism by which TNIP1 variants may contribute to SLE pathogenesis.
- Published
- 2012
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