2,181 results on '"Langefeld, Carl D."'
Search Results
52. Improved Performance of Dynamic Measures of Insulin Response Over Surrogate Indices to Identify Genetic Contributors of Type 2 Diabetes: The GUARDIAN Consortium
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Palmer, Nicholette D, Wagenknecht, Lynne E, Langefeld, Carl D, Wang, Nan, Buchanan, Thomas A, Xiang, Anny H, Allayee, Hooman, Bergman, Richard N, Raffel, Leslie J, Chen, Yii-Der Ida, Haritunians, Talin, Fingerlin, Tasha, Goodarzi, Mark O, Taylor, Kent D, Rotter, Jerome I, Watanabe, Richard M, and Bowden, Donald W
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Biomedical and Clinical Sciences ,Genetics ,Diabetes ,Metabolic and endocrine ,Adult ,Aged ,Blood Glucose ,Diabetes Mellitus ,Type 2 ,Female ,Glucose Tolerance Test ,Homeostasis ,Humans ,Insulin ,Insulin Resistance ,Male ,Middle Aged ,Medical and Health Sciences ,Endocrinology & Metabolism ,Biomedical and clinical sciences - Abstract
Type 2 diabetes (T2D) is a heterogeneous disorder with contributions from peripheral insulin resistance and β-cell dysfunction. For minimization of phenotypic heterogeneity, quantitative intermediate phenotypes characterizing basal glucose homeostasis (insulin resistance and HOMA of insulin resistance [HOMAIR] and of β-cell function [HOMAB]) have shown promise in relatively large samples. We investigated the utility of dynamic measures of glucose homeostasis (insulin sensitivity [SI] and acute insulin response [AIRg]) evaluating T2D-susceptibility variants (n = 57) in Hispanic Americans from the GUARDIAN Consortium (n = 2,560). Basal and dynamic measures were genetically correlated (HOMAB-AIRg: ρG = 0.28-0.73; HOMAIR-SI: ρG = -0.73 to -0.83) with increased heritability for the dynamic measure AIRg Significant association of variants with dynamic measures (P < 8.77 × 10(-4)) was observed. A pattern of superior performance of AIRg was observed for well-established loci including MTNR1B (P = 9.46 × 10(-12)), KCNQ1 (P = 1.35 × 10(-4)), and TCF7L2 (P = 5.10 × 10(-4)) with study-wise statistical significance. Notably, significant association of MTNR1B with AIRg (P < 1.38 × 10(-9)) was observed in a population one-fourteenth the size of the initial discovery cohort. These observations suggest that basal and dynamic measures provide different views and levels of sensitivity to discrete elements of glucose homeostasis. Although more costly to obtain, dynamic measures yield significant results that could be considered physiologically "closer" to causal pathways and provide insight into the discrete mechanisms of action.
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- 2016
53. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin
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Liu, Ching-Ti, Raghavan, Sridharan, Maruthur, Nisa, Kabagambe, Edmond Kato, Hong, Jaeyoung, Ng, Maggie CY, Hivert, Marie-France, Lu, Yingchang, An, Ping, Bentley, Amy R, Drolet, Anne M, Gaulton, Kyle J, Guo, Xiuqing, Armstrong, Loren L, Irvin, Marguerite R, Li, Man, Lipovich, Leonard, Rybin, Denis V, Taylor, Kent D, Agyemang, Charles, Palmer, Nicholette D, Cade, Brian E, Chen, Wei-Min, Dauriz, Marco, Delaney, Joseph AC, Edwards, Todd L, Evans, Daniel S, Evans, Michele K, Lange, Leslie A, Leong, Aaron, Liu, Jingmin, Liu, Yongmei, Nayak, Uma, Patel, Sanjay R, Porneala, Bianca C, Rasmussen-Torvik, Laura J, Snijder, Marieke B, Stallings, Sarah C, Tanaka, Toshiko, Yanek, Lisa R, Zhao, Wei, Becker, Diane M, Bielak, Lawrence F, Biggs, Mary L, Bottinger, Erwin P, Bowden, Donald W, Chen, Guanjie, Correa, Adolfo, Couper, David J, Crawford, Dana C, Cushman, Mary, Eicher, John D, Fornage, Myriam, Franceschini, Nora, Fu, Yi-Ping, Goodarzi, Mark O, Gottesman, Omri, Hara, Kazuo, Harris, Tamara B, Jensen, Richard A, Johnson, Andrew D, Jhun, Min A, Karter, Andrew J, Keller, Margaux F, Kho, Abel N, Kizer, Jorge R, Krauss, Ronald M, Langefeld, Carl D, Li, Xiaohui, Liang, Jingling, Liu, Simin, Lowe, William L, Mosley, Thomas H, North, Kari E, Pacheco, Jennifer A, Peyser, Patricia A, Patrick, Alan L, Rice, Kenneth M, Selvin, Elizabeth, Sims, Mario, Smith, Jennifer A, Tajuddin, Salman M, Vaidya, Dhananjay, Wren, Mary P, Yao, Jie, Zhu, Xiaofeng, Ziegler, Julie T, Zmuda, Joseph M, Zonderman, Alan B, Zwinderman, Aeilko H, Consortium, AAAG, Consortium, CARe, Consortium, COGENT-BP, Consortium, eMERGE, Consortium, MEDIA, Adeyemo, Adebowale, Boerwinkle, Eric, Ferrucci, Luigi, Hayes, M Geoffrey, and Kardia, Sharon LR
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Health Disparities ,Human Genome ,Diabetes ,Minority Health ,Metabolic and endocrine ,Asian People ,Black People ,Blood Glucose ,Diabetes Mellitus ,Type 2 ,Enhancer Elements ,Genetic ,Ethnicity ,Fasting ,Female ,Gene Frequency ,Genome-Wide Association Study ,Humans ,Insulin ,Insulin Resistance ,Introns ,Islets of Langerhans ,Male ,Molecular Sequence Annotation ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Racial Groups ,Transcription Factors ,White People ,AAAG Consortium ,CARe Consortium ,COGENT-BP Consortium ,eMERGE Consortium ,MEDIA Consortium ,MAGIC Consortium ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.
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- 2016
54. A Novel Metastatic Estrogen Receptor-Expressing Breast Cancer Model with Antiestrogen Responsiveness
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Langsten, Kendall L., primary, Shi, Lihong, additional, Wilson, Adam S., additional, Lumia, Salvatore, additional, Westwood, Brian, additional, Skeen, Alexandra M., additional, Xie, Maria T., additional, Surratt, Victoria E., additional, Turner, JoLyn, additional, Langefeld, Carl D., additional, Singh, Ravi, additional, Cook, Katherine L., additional, and Kerr, Bethany A., additional
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- 2023
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55. A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs
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Venema, Wouter J., primary, Hiddingh, Sanne, additional, van Loosdregt, Jorg, additional, Bowes, John, additional, Balliu, Brunilda, additional, de Boer, Joke H., additional, Ossewaarde-van Norel, Jeannette, additional, Thompson, Susan D., additional, Langefeld, Carl D., additional, de Ligt, Aafke, additional, van der Veken, Lars T., additional, Krijger, Peter H.L., additional, de Laat, Wouter, additional, and Kuiper, Jonas J.W., additional
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- 2023
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56. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci
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de las Fuentes, Lisa, primary, Schwander, Karen L., additional, Brown, Michael R., additional, Bentley, Amy R., additional, Winkler, Thomas W., additional, Sung, Yun Ju, additional, Munroe, Patricia B., additional, Miller, Clint L., additional, Aschard, Hugo, additional, Aslibekyan, Stella, additional, Bartz, Traci M., additional, Bielak, Lawrence F., additional, Chai, Jin Fang, additional, Cheng, Ching-Yu, additional, Dorajoo, Rajkumar, additional, Feitosa, Mary F., additional, Guo, Xiuqing, additional, Hartwig, Fernando P., additional, Horimoto, Andrea, additional, Kolčić, Ivana, additional, Lim, Elise, additional, Liu, Yongmei, additional, Manning, Alisa K., additional, Marten, Jonathan, additional, Musani, Solomon K., additional, Noordam, Raymond, additional, Padmanabhan, Sandosh, additional, Rankinen, Tuomo, additional, Richard, Melissa A., additional, Ridker, Paul M., additional, Smith, Albert V., additional, Vojinovic, Dina, additional, Zonderman, Alan B., additional, Alver, Maris, additional, Boissel, Mathilde, additional, Christensen, Kaare, additional, Freedman, Barry I., additional, Gao, Chuan, additional, Giulianini, Franco, additional, Harris, Sarah E., additional, He, Meian, additional, Hsu, Fang-Chi, additional, Kühnel, Brigitte, additional, Laguzzi, Federica, additional, Li, Xiaoyin, additional, Lyytikäinen, Leo-Pekka, additional, Nolte, Ilja M., additional, Poveda, Alaitz, additional, Rauramaa, Rainer, additional, Riaz, Muhammad, additional, Robino, Antonietta, additional, Sofer, Tamar, additional, Takeuchi, Fumihiko, additional, Tayo, Bamidele O., additional, van der Most, Peter J., additional, Verweij, Niek, additional, Ware, Erin B., additional, Weiss, Stefan, additional, Wen, Wanqing, additional, Yanek, Lisa R., additional, Zhan, Yiqiang, additional, Amin, Najaf, additional, Arking, Dan E., additional, Ballantyne, Christie, additional, Boerwinkle, Eric, additional, Brody, Jennifer A., additional, Broeckel, Ulrich, additional, Campbell, Archie, additional, Canouil, Mickaël, additional, Chai, Xiaoran, additional, Chen, Yii-Der Ida, additional, Chen, Xu, additional, Chitrala, Kumaraswamy Naidu, additional, Concas, Maria Pina, additional, de Faire, Ulf, additional, de Mutsert, Renée, additional, de Silva, H. Janaka, additional, de Vries, Paul S., additional, Do, Ahn, additional, Faul, Jessica D., additional, Fisher, Virginia, additional, Floyd, James S., additional, Forrester, Terrence, additional, Friedlander, Yechiel, additional, Girotto, Giorgia, additional, Gu, C. Charles, additional, Hallmans, Göran, additional, Heikkinen, Sami, additional, Heng, Chew-Kiat, additional, Homuth, Georg, additional, Hunt, Steven, additional, Ikram, M. Arfan, additional, Jacobs, David R., additional, Kavousi, Maryam, additional, Khor, Chiea Chuen, additional, Kilpeläinen, Tuomas O., additional, Koh, Woon-Puay, additional, Komulainen, Pirjo, additional, Langefeld, Carl D., additional, Liang, Jingjing, additional, Liu, Kiang, additional, Liu, Jianjun, additional, Lohman, Kurt, additional, Mägi, Reedik, additional, Manichaikul, Ani W., additional, McKenzie, Colin A., additional, Meitinger, Thomas, additional, Milaneschi, Yuri, additional, Nauck, Matthias, additional, Nelson, Christopher P., additional, O’Connell, Jeffrey R., additional, Palmer, Nicholette D., additional, Pereira, Alexandre C., additional, Perls, Thomas, additional, Peters, Annette, additional, Polašek, Ozren, additional, Raitakari, Olli T., additional, Rice, Kenneth, additional, Rice, Treva K., additional, Rich, Stephen S., additional, Sabanayagam, Charumathi, additional, Schreiner, Pamela J., additional, Shu, Xiao-Ou, additional, Sidney, Stephen, additional, Sims, Mario, additional, Smith, Jennifer A., additional, Starr, John M., additional, Strauch, Konstantin, additional, Tai, E. Shyong, additional, Taylor, Kent D., additional, Tsai, Michael Y., additional, Uitterlinden, André G., additional, van Heemst, Diana, additional, Waldenberger, Melanie, additional, Wang, Ya-Xing, additional, Wei, Wen-Bin, additional, Wilson, Gregory, additional, Xuan, Deng, additional, Yao, Jie, additional, Yu, Caizheng, additional, Yuan, Jian-Min, additional, Zhao, Wei, additional, Becker, Diane M., additional, Bonnefond, Amélie, additional, Bowden, Donald W., additional, Cooper, Richard S., additional, Deary, Ian J., additional, Divers, Jasmin, additional, Esko, Tõnu, additional, Franks, Paul W., additional, Froguel, Philippe, additional, Gieger, Christian, additional, Jonas, Jost B., additional, Kato, Norihiro, additional, Lakka, Timo A., additional, Leander, Karin, additional, Lehtimäki, Terho, additional, Magnusson, Patrik K. E., additional, North, Kari E., additional, Ntalla, Ioanna, additional, Penninx, Brenda, additional, Samani, Nilesh J., additional, Snieder, Harold, additional, Spedicati, Beatrice, additional, van der Harst, Pim, additional, Völzke, Henry, additional, Wagenknecht, Lynne E., additional, Weir, David R., additional, Wojczynski, Mary K., additional, Wu, Tangchun, additional, Zheng, Wei, additional, Zhu, Xiaofeng, additional, Bouchard, Claude, additional, Chasman, Daniel I., additional, Evans, Michele K., additional, Fox, Ervin R., additional, Gudnason, Vilmundur, additional, Hayward, Caroline, additional, Horta, Bernardo L., additional, Kardia, Sharon L. R., additional, Krieger, Jose Eduardo, additional, Mook-Kanamori, Dennis O., additional, Peyser, Patricia A., additional, Province, Michael M., additional, Psaty, Bruce M., additional, Rudan, Igor, additional, Sim, Xueling, additional, Smith, Blair H., additional, van Dam, Rob M., additional, van Duijn, Cornelia M., additional, Wong, Tien Yin, additional, Arnett, Donna K., additional, Rao, Dabeeru C., additional, Gauderman, James, additional, Liu, Ching-Ti, additional, Morrison, Alanna C., additional, Rotter, Jerome I., additional, and Fornage, Myriam, additional
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- 2023
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57. Deep Resequencing of the 1q22 Locus in Non‐Lobar Intracerebral Hemorrhage
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Parodi, Livia, primary, Comeau, Mary E., additional, Georgakis, Marios K., additional, Mayerhofer, Ernst, additional, Chung, Jaeyoon, additional, Falcone, Guido J., additional, Malik, Rainer, additional, Demel, Stacie L., additional, Worrall, Bradford B., additional, Koch, Sebastian, additional, Testai, Fernando D., additional, Kittner, Steven J., additional, McCauley, Jacob L., additional, Hall, Christiana E., additional, Mayson, Douglas J., additional, Elkind, Mitchell S.V., additional, James, Michael L., additional, Woo, Daniel, additional, Rosand, Jonathan, additional, Langefeld, Carl D., additional, and Anderson, Christopher D., additional
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- 2023
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58. Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus
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Zhao, Jian, Wu, Hui, Langefeld, Carl D, Kaufman, Kenneth M, Kelly, Jennifer A, Bae, Sang-Cheol, networks, Marta E Alarcón-Riquelme for the BIOLUPUS and GENLES, Alarcón, Graciela S, Anaya, Juan-Manuel, Criswell, Lindsey A, Freedman, Barry I, Kamen, Diane L, Gilkeson, Gary S, Jacob, Chaim O, James, Judith A, Merrill, Joan T, Gaffney, Patrick M, Sivils, Kathy Moser, Niewold, Timothy B, Petri, Michelle A, Song, Seung Taek, Jeong, Hye-jin, Ramsey-Goldman, Rosalind, Reveille, John D, Scofield, R Hal, Stevens, Anne M, Boackle, Susan A, Vilá, Luis M, Chang, Deh-Ming, Song, Yeong Wook, Vyse, Timothy J, Harley, John B, Brown, Elizabeth E, Edberg, Jeffrey C, Kimberly, Robert P, Hahn, Bevra H, Grossman, Jennifer M, Tsao, Betty P, and La Cava, Antonio
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Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,Autoimmune Disease ,Genetic Testing ,Genetics ,Lupus ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Case-Control Studies ,Genetic Predisposition to Disease ,Genotype ,Humans ,Leptin ,Lupus Erythematosus ,Systemic ,Polymorphism ,Single Nucleotide ,Systemic lupus erythematosus ,Leptin pathway ,Gene polymorphisms ,Marta E. Alarcón-Riquelme for the BIOLUPUS and GENLES networks - Abstract
Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE.
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- 2015
59. Hierarchicell: an R-package for estimating power for tests of differential expression with single-cell data
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Zimmerman, Kip D. and Langefeld, Carl D.
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- 2021
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60. A practical solution to pseudoreplication bias in single-cell studies
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Zimmerman, Kip D., Espeland, Mark A., and Langefeld, Carl D.
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- 2021
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61. Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes
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Ghodke-Puranik, Yogita, Jin, Zhongbo, Zimmerman, Kip D., Ainsworth, Hannah C., Fan, Wei, Jensen, Mark A., Dorschner, Jessica M., Vsetecka, Danielle M., Amin, Shreyasee, Makol, Ashima, Ernste, Floranne, Osborn, Thomas, Moder, Kevin, Chowdhary, Vaidehi, Langefeld, Carl D., and Niewold, Timothy B.
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- 2021
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62. Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).
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Iyengar, Sudha K, Sedor, John R, Freedman, Barry I, Kao, WH Linda, Kretzler, Matthias, Keller, Benjamin J, Abboud, Hanna E, Adler, Sharon G, Best, Lyle G, Bowden, Donald W, Burlock, Allison, Chen, Yii-Der Ida, Cole, Shelley A, Comeau, Mary E, Curtis, Jeffrey M, Divers, Jasmin, Drechsler, Christiane, Duggirala, Ravi, Elston, Robert C, Guo, Xiuqing, Huang, Huateng, Hoffmann, Michael Marcus, Howard, Barbara V, Ipp, Eli, Kimmel, Paul L, Klag, Michael J, Knowler, William C, Kohn, Orly F, Leak, Tennille S, Leehey, David J, Li, Man, Malhotra, Alka, März, Winfried, Nair, Viji, Nelson, Robert G, Nicholas, Susanne B, O'Brien, Stephen J, Pahl, Madeleine V, Parekh, Rulan S, Pezzolesi, Marcus G, Rasooly, Rebekah S, Rotimi, Charles N, Rotter, Jerome I, Schelling, Jeffrey R, Seldin, Michael F, Shah, Vallabh O, Smiles, Adam M, Smith, Michael W, Taylor, Kent D, Thameem, Farook, Thornley-Brown, Denyse P, Truitt, Barbara J, Wanner, Christoph, Weil, E Jennifer, Winkler, Cheryl A, Zager, Philip G, Igo, Robert P, Hanson, Robert L, Langefeld, Carl D, and Family Investigation of Nephropathy and Diabetes (FIND)
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Family Investigation of Nephropathy and Diabetes ,Humans ,Diabetic Nephropathies ,Diabetes Mellitus ,Type 2 ,Genetic Predisposition to Disease ,RNA-Binding Proteins ,African Americans ,Indians ,North American ,European Continental Ancestry Group ,Hispanic Americans ,United States ,Genome-Wide Association Study ,Diabetes ,Genetics ,Human Genome ,Clinical Research ,Kidney Disease ,American Indian or Alaska Native ,Prevention ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Renal and urogenital ,Developmental Biology - Abstract
Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.
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- 2015
63. Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans
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Carty, Cara L, Keene, Keith L, Cheng, Yu-Ching, Meschia, James F, Chen, Wei-Min, Nalls, Mike, Bis, Joshua C, Kittner, Steven J, Rich, Stephen S, Tajuddin, Salman, Zonderman, Alan B, Evans, Michele K, Langefeld, Carl D, Gottesman, Rebecca, Mosley, Thomas H, Shahar, Eyal, Woo, Daniel, Yaffe, Kristine, Liu, Yongmei, Sale, Michèle M, Dichgans, Martin, Malik, Rainer, Longstreth, WT, Mitchell, Braxton D, Psaty, Bruce M, Kooperberg, Charles, Reiner, Alexander, Worrall, Bradford B, and Fornage, Myriam
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Human Genome ,Stroke ,Brain Disorders ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,African Americans ,Case-Control Studies ,Cohort Studies ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Polymorphism ,Single Nucleotide ,Risk Factors ,genetic association studies ,genome-wide association study ,meta-analysis ,stroke ,COMPASS and METASTROKE Consortia ,Black or African American ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Neurosciences ,Neurology & Neurosurgery - Abstract
Background and purposeThe majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations.MethodsUsing METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with P
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- 2015
64. Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression
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Lu, Xiaoming, Zoller, Erin E, Weirauch, Matthew T, Wu, Zhiguo, Namjou, Bahram, Williams, Adrienne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, Glenn, Stuart B, Adler, Adam, Shen, Nan, Nath, Swapan K, Stevens, Anne M, Freedman, Barry I, Tsao, Betty P, Jacob, Chaim O, Kamen, Diane L, Brown, Elizabeth E, Gilkeson, Gary S, Alarcón, Graciela S, Reveille, John D, Anaya, Juan-Manuel, James, Judith A, Sivils, Kathy L, Criswell, Lindsey A, Vilá, Luis M, Alarcón-Riquelme, Marta E, Petri, Michelle, Scofield, R Hal, Kimberly, Robert P, Ramsey-Goldman, Rosalind, Bin Joo, Young, Choi, Jeongim, Bae, Sang-Cheol, Boackle, Susan A, Graham, Deborah Cunninghame, Vyse, Timothy J, Guthridge, Joel M, Gaffney, Patrick M, Langefeld, Carl D, Kelly, Jennifer A, Greis, Kenneth D, Kaufman, Kenneth M, Harley, John B, and Kottyan, Leah C
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Biotechnology ,Lupus ,Autoimmune Disease ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Alleles ,Animals ,Asian People ,Bayes Theorem ,Genetic Predisposition to Disease ,Genotype ,Haplotypes ,Humans ,Lupus Erythematosus ,Systemic ,Mice ,Protein Binding ,Proto-Oncogene Protein c-ets-1 ,STAT1 Transcription Factor ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1.
- Published
- 2015
65. Genetic Variants Associated With Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium
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Palmer, Nicholette D, Goodarzi, Mark O, Langefeld, Carl D, Wang, Nan, Guo, Xiuqing, Taylor, Kent D, Fingerlin, Tasha E, Norris, Jill M, Buchanan, Thomas A, Xiang, Anny H, Haritunians, Talin, Ziegler, Julie T, Williams, Adrienne H, Stefanovski, Darko, Cui, Jinrui, Mackay, Adrienne W, Henkin, Leora F, Bergman, Richard N, Gao, Xiaoyi, Gauderman, James, Varma, Rohit, Hanis, Craig L, Cox, Nancy J, Highland, Heather M, Below, Jennifer E, Williams, Amy L, Burtt, Noel P, Aguilar-Salinas, Carlos A, Huerta-Chagoya, Alicia, Gonzalez-Villalpando, Clicerio, Orozco, Lorena, Haiman, Christopher A, Tsai, Michael Y, Johnson, W Craig, Yao, Jie, Rasmussen-Torvik, Laura, Pankow, James, Snively, Beverly, Jackson, Rebecca D, Liu, Simin, Nadler, Jerry L, Kandeel, Fouad, Chen, Yii-Der I, Bowden, Donald W, Rich, Stephen S, Raffel, Leslie J, Rotter, Jerome I, Watanabe, Richard M, and Wagenknecht, Lynne E
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Biomedical and Clinical Sciences ,Obesity ,Clinical Research ,Diabetes ,Human Genome ,Genetics ,Metabolic and endocrine ,Blood Glucose ,Databases ,Factual ,Diabetes Mellitus ,Type 2 ,Gene Expression Regulation ,Genetic Variation ,Genome ,Genome-Wide Association Study ,Genotype ,Hispanic or Latino ,Homeostasis ,Humans ,Medical and Health Sciences ,Endocrinology & Metabolism ,Biomedical and clinical sciences - Abstract
Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D.
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- 2015
66. Empirical characteristics of family-based linkage to a complex trait: the ADIPOQ region and adiponectin levels
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Hellwege, Jacklyn N, Palmer, Nicholette D, Brown, Mark W, Ziegler, Julie T, An, Sandy S, Guo, Xiuqing, Chen, Ida Y-D, Taylor, Kent, Hawkins, Gregory A, Ng, Maggie CY, Speliotes, Elizabeth K, Lorenzo, Carlos, Norris, Jill M, Rotter, Jerome I, Wagenknecht, Lynne E, Langefeld, Carl D, and Bowden, Donald W
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Biological Sciences ,Genetics ,Human Genome ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Adiponectin ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Databases ,Nucleic Acid ,Datasets as Topic ,Family ,Female ,Genetic Linkage ,Genetic Loci ,Hispanic or Latino ,Humans ,Lod Score ,Male ,Microsatellite Repeats ,Middle Aged ,Polymorphism ,Single Nucleotide ,Complementary and Alternative Medicine ,Paediatrics and Reproductive Medicine ,Genetics & Heredity ,Reproductive medicine - Abstract
We previously identified a low-frequency (1.1 %) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD = 8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common variants, exome chip genotyping, and genome-wide association study data to detect linkage and association to adiponectin protein levels at this locus. Simple two-point linkage and association analyses were performed in 88 Hispanic families (1,150 individuals) using 10,958 SNPs on chromosome 3. Approaches were compared for their ability to map the functional variant, G45R, which was strongly linked (two-point LOD = 20.98) and powerfully associated (p value = 8.1 × 10(-50)). Over 450 SNPs within a broad 61 Mb interval around rs200573126 showed nominal evidence of linkage (LOD > 3) but only four other SNPs in this region were associated with p values
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- 2015
67. The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share
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Kottyan, Leah C, Zoller, Erin E, Bene, Jessica, Lu, Xiaoming, Kelly, Jennifer A, Rupert, Andrew M, Lessard, Christopher J, Vaughn, Samuel E, Marion, Miranda, Weirauch, Matthew T, Namjou, Bahram, Adler, Adam, Rasmussen, Astrid, Glenn, Stuart, Montgomery, Courtney G, Hirschfield, Gideon M, Xie, Gang, Coltescu, Catalina, Amos, Chris, Li, He, Ice, John A, Nath, Swapan K, Mariette, Xavier, Bowman, Simon, Rischmueller, Maureen, Lester, Sue, Brun, Johan G, Gøransson, Lasse G, Harboe, Erna, Omdal, Roald, Cunninghame-Graham, Deborah S, Vyse, Tim, Miceli-Richard, Corinne, Brennan, Michael T, Lessard, James A, Wahren-Herlenius, Marie, Kvarnström, Marika, Illei, Gabor G, Witte, Torsten, Jonsson, Roland, Eriksson, Per, Nordmark, Gunnel, Ng, Wan-Fai, Anaya, Juan-Manuel, Rhodus, Nelson L, Segal, Barbara M, Merrill, Joan T, James, Judith A, Guthridge, Joel M, Scofield, R Hal, Alarcon-Riquelme, Marta, Bae, Sang-Cheol, Boackle, Susan A, Criswell, Lindsey A, Gilkeson, Gary, Kamen, Diane L, Jacob, Chaim O, Kimberly, Robert, Brown, Elizabeth, Edberg, Jeffrey, Alarcón, Graciela S, Reveille, John D, Vilá, Luis M, Petri, Michelle, Ramsey-Goldman, Rosalind, Freedman, Barry I, Niewold, Timothy, Stevens, Anne M, Tsao, Betty P, Ying, Jun, Mayes, Maureen D, Gorlova, Olga Y, Wakeland, Ward, Radstake, Timothy, Martin, Ezequiel, Martin, Javier, Siminovitch, Katherine, Sivils, Kathy L Moser, Gaffney, Patrick M, Langefeld, Carl D, Harley, John B, and Kaufman, Kenneth M
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Biological Sciences ,Genetics ,Autoimmune Disease ,Biotechnology ,Lupus ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Autoimmune Diseases ,Bayes Theorem ,Case-Control Studies ,Cohort Studies ,DNA-Binding Proteins ,Haplotypes ,Humans ,Interferon Regulatory Factors ,Lupus Erythematosus ,Systemic ,Male ,Polymorphism ,Single Nucleotide ,Promoter Regions ,Genetic ,beta Karyopherins ,UK Primary Sjögren's Syndrome Registry ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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- 2015
68. A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)
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Gao, Chuan, Wang, Nan, Guo, Xiuqing, Ziegler, Julie T, Taylor, Kent D, Xiang, Anny H, Hai, Yang, Kridel, Steven J, Nadler, Jerry L, Kandeel, Fouad, Raffel, Leslie J, Chen, Yii-Der I, Norris, Jill M, Rotter, Jerome I, Watanabe, Richard M, Wagenknecht, Lynne E, Bowden, Donald W, Speliotes, Elizabeth K, Goodarzi, Mark O, Langefeld, Carl D, and Palmer, Nicholette D
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Clinical Research ,Nutrition ,Aging ,Prevention ,Human Genome ,Obesity ,Aetiology ,2.1 Biological and endogenous factors ,Cardiovascular ,Oral and gastrointestinal ,Stroke ,Metabolic and endocrine ,Cancer ,Adiposity ,Genetic Association Studies ,Genetic Predisposition to Disease ,Hispanic or Latino ,Humans ,Isocitrate Dehydrogenase ,Membrane Proteins ,Polymorphism ,Single Nucleotide ,General Science & Technology - Abstract
Obesity is growing epidemic affecting 35% of adults in the United States. Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we report the results from genome-wide and exome chip association studies focusing on total body measures of adiposity including body mass index (BMI), percent body fat (PBF) and measures of fat deposition including waist circumference (WAIST), waist-hip ratio (WHR), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in Hispanic Americans (nmax = 1263) from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Five SNPs from two novel loci attained genome-wide significance (P
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- 2015
69. Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial
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Langefeld, Carl D, Divers, Jasmin, Pajewski, Nicholas M, Hawfield, Amret T, Reboussin, David M, Bild, Diane E, Kaysen, George A, Kimmel, Paul L, Raj, Dominic S, Ricardo, Ana C, Wright, Jackson T, Sedor, John R, Rocco, Michael V, Freedman, Barry I, and Trial, on behalf of the Systolic Blood Pressure Intervention
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Hypertension ,Cardiovascular ,Kidney Disease ,Clinical Trials and Supportive Activities ,Atherosclerosis ,Heart Disease ,Prevention ,Clinical Research ,Renal and urogenital ,Good Health and Well Being ,African Americans ,Apolipoprotein L1 ,Apolipoproteins ,Cardiovascular Diseases ,Female ,Genetic Variation ,Humans ,Lipoproteins ,HDL ,Male ,Middle Aged ,Renal Insufficiency ,Chronic ,Systolic Blood Pressure Intervention Trial ,Black or African American ,Clinical Sciences ,Urology & Nephrology - Abstract
Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (β) 0.33) and negatively associated with eGFR (β -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g.
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- 2015
70. SMIM1 absence is associated with reduced energy expenditure and excess weight
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Banasik, Karina, Bay, Jakob, Boldsen, Jens Kjærgaard, Brodersen, Thorsten, Brunak, Søren, Burgdorf, Kristoffer, Chalmer, Mona Ameri, Didriksen, Maria, Dinh, Khoa Manh, Dowsett, Joseph, Erikstrup, Christian, Feenstra, Bjarke, Geller, Frank, Gudbjartsson, Daniel, Hansen, Thomas Folkmann, Hindhede, Lotte, Hjalgrim, Henrik, Jacobsen, Rikke Louise, Jemec, Gregor, Jensen, Bitten Aagaard, Kaspersen, Katrine, Kjerulff, Bertram Dalskov, Kogelman, Lisette, Hørup Larsen, Margit Anita, Louloudis, Ioannis, Lundgaard, Agnete, Susan, Mikkelsen, Christina, Nissen, Ioanna, Nyegaard, Mette, Ostrowski, Sisse Rye, Pedersen, Ole Birger, Henriksen, Alexander Pil, Rohde, Palle Duun, Rostgaard, Klaus, Schwinn, Michael, Stefansson, Kari, Stefánsson, Hreinn, Sørensen, Erik, þorsteinsdóttir, Unnur, Thørner, Lise Wegner, Bruun, Mie Topholm, Ullum, Henrik, Werge, Thomas, Westergaard, David, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian’an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Katie Chan, Kei Hang, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Loz, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V.R., Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P., Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Southam, Lorraine, Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J.L., Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J.C., Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M. Arfan, Johnson, W. Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R.H.J., Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, Van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Goncalo R., Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Ida Chen, Yii-Der, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, Janaka de Silva, H., Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J. Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L.R., Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J.F., Magnusson, Patrik K.E., Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P. Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I.A., Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E. Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G.M., Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C.J., Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Stefanucci, Luca, Moslemi, Camous, Tomé, Ana R., Virtue, Samuel, Bidault, Guillaume, Gleadall, Nicholas S., Watson, Laura P.E., Kwa, Jing E., Burden, Frances, Farrow, Samantha, Võsa, Urmo, Burling, Keith, Walker, Lindsay, Ord, John, Barker, Peter, Warner, James, Frary, Amy, Renhstrom, Karola, Ashford, Sofie E., Piper, Jo, Biggs, Gail, Erber, Wendy N., Hoffman, Gary J., Schoenmakers, Nadia, Rieneck, Klaus, Dziegiel, Morten H., Azzu, Vian, Vacca, Michele, Aparicio, Hugo Javier, Hui, Qin, Cho, Kelly, Sun, Yan V., Wilson, Peter W., Bayraktar, Omer A., Vidal-Puig, Antonio, Ostrowski, Sisse R., Astle, William J., Olsson, Martin L., Storry, Jill R., Pedersen, Ole B., Ouwehand, Willem H., Chatterjee, Krishna, Vuckovic, Dragana, and Frontini, Mattia
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- 2024
- Full Text
- View/download PDF
71. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.
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Ng, Maggie CY, Shriner, Daniel, Chen, Brian H, Li, Jiang, Chen, Wei-Min, Guo, Xiuqing, Liu, Jiankang, Bielinski, Suzette J, Yanek, Lisa R, Nalls, Michael A, Comeau, Mary E, Rasmussen-Torvik, Laura J, Jensen, Richard A, Evans, Daniel S, Sun, Yan V, An, Ping, Patel, Sanjay R, Lu, Yingchang, Long, Jirong, Armstrong, Loren L, Wagenknecht, Lynne, Yang, Lingyao, Snively, Beverly M, Palmer, Nicholette D, Mudgal, Poorva, Langefeld, Carl D, Keene, Keith L, Freedman, Barry I, Mychaleckyj, Josyf C, Nayak, Uma, Raffel, Leslie J, Goodarzi, Mark O, Chen, Y-D Ida, Taylor, Herman A, Correa, Adolfo, Sims, Mario, Couper, David, Pankow, James S, Boerwinkle, Eric, Adeyemo, Adebowale, Doumatey, Ayo, Chen, Guanjie, Mathias, Rasika A, Vaidya, Dhananjay, Singleton, Andrew B, Zonderman, Alan B, Igo, Robert P, Sedor, John R, FIND Consortium, Kabagambe, Edmond K, Siscovick, David S, McKnight, Barbara, Rice, Kenneth, Liu, Yongmei, Hsueh, Wen-Chi, Zhao, Wei, Bielak, Lawrence F, Kraja, Aldi, Province, Michael A, Bottinger, Erwin P, Gottesman, Omri, Cai, Qiuyin, Zheng, Wei, Blot, William J, Lowe, William L, Pacheco, Jennifer A, Crawford, Dana C, eMERGE Consortium, DIAGRAM Consortium, Grundberg, Elin, MuTHER Consortium, Rich, Stephen S, Hayes, M Geoffrey, Shu, Xiao-Ou, Loos, Ruth JF, Borecki, Ingrid B, Peyser, Patricia A, Cummings, Steven R, Psaty, Bruce M, Fornage, Myriam, Iyengar, Sudha K, Evans, Michele K, Becker, Diane M, Kao, WH Linda, Wilson, James G, Rotter, Jerome I, Sale, Michèle M, Liu, Simin, Rotimi, Charles N, Bowden, Donald W, and MEta-analysis of type 2 DIabetes in African Americans Consortium
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FIND Consortium ,eMERGE Consortium ,DIAGRAM Consortium ,MuTHER Consortium ,MEta-analysis of type 2 DIabetes in African Americans Consortium ,Humans ,Diabetes Mellitus ,Type 2 ,HMGA2 Protein ,HLA-B27 Antigen ,Polymorphism ,Single Nucleotide ,African Americans ,Mutant Chimeric Proteins ,KCNQ1 Potassium Channel ,Genome-Wide Association Study ,Transcription Factor 7-Like 2 Protein ,Human Genome ,Diabetes ,Genetics ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Developmental Biology - Abstract
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)
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- 2014
72. Genome‐Wide Family‐Based Linkage Analysis of Exome Chip Variants and Cardiometabolic Risk
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Hellwege, Jacklyn N, Palmer, Nicholette D, Raffield, Laura M, Ng, Maggie CY, Hawkins, Gregory A, Long, Jirong, Lorenzo, Carlos, Norris, Jill M, Chen, Y‐D Ida, Speliotes, Elizabeth K, Rotter, Jerome I, Langefeld, Carl D, Wagenknecht, Lynne E, and Bowden, Donald W
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Clinical Research ,Cardiovascular ,Atherosclerosis ,Adolescent ,Adult ,Black or African American ,Aged ,Aged ,80 and over ,Apolipoproteins ,Cholesterol Ester Transfer Proteins ,Exome ,Female ,Genetic Linkage ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Hispanic or Latino ,Humans ,Insulin Resistance ,Lipoproteins ,HDL ,Lod Score ,Male ,Middle Aged ,Oligonucleotide Array Sequence Analysis ,Phenotype ,Polymorphism ,Single Nucleotide ,Young Adult ,African American ,Hispanic ,genetic variance ,Public Health and Health Services - Abstract
Linkage analysis of complex traits has had limited success in identifying trait-influencing loci. Recently, coding variants have been implicated as the basis for some biomedical associations. We tested whether coding variants are the basis for linkage peaks of complex traits in 42 African-American (n = 596) and 90 Hispanic (n = 1,414) families in the Insulin Resistance Atherosclerosis Family Study (IRASFS) using Illumina HumanExome Beadchips. A total of 92,157 variants in African Americans (34%) and 81,559 (31%) in Hispanics were polymorphic and tested using two-point linkage and association analyses with 37 cardiometabolic phenotypes. In African Americans 77 LOD scores greater than 3 were observed. The highest LOD score was 4.91 with the APOE SNP rs7412 (MAF = 0.13) with plasma apolipoprotein B (ApoB). This SNP was associated with ApoB (P-value = 4 × 10(-19)) and accounted for 16.2% of the variance in African Americans. In Hispanic families, 104 LOD scores were greater than 3. The strongest evidence of linkage (LOD = 4.29) was with rs5882 (MAF = 0.46) in CETP with HDL. CETP variants were strongly associated with HDL (0.00049 < P-value
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- 2014
73. Two Functional Lupus-Associated BLK Promoter Variants Control Cell-Type- and Developmental-Stage-Specific Transcription
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Guthridge, Joel M, Lu, Rufei, Sun, Harry, Sun, Celi, Wiley, Graham B, Dominguez, Nicolas, Macwana, Susan R, Lessard, Christopher J, Kim-Howard, Xana, Cobb, Beth L, Kaufman, Kenneth M, Kelly, Jennifer A, Langefeld, Carl D, Adler, Adam J, Harley, Isaac TW, Merrill, Joan T, Gilkeson, Gary S, Kamen, Diane L, Niewold, Timothy B, Brown, Elizabeth E, Edberg, Jeffery C, Petri, Michelle A, Ramsey-Goldman, Rosalind, Reveille, John D, Vilá, Luis M, Kimberly, Robert P, Freedman, Barry I, Stevens, Anne M, Boackle, Susan A, Criswell, Lindsey A, Vyse, Tim J, Behrens, Timothy W, Jacob, Chaim O, Alarcón-Riquelme, Marta E, Sivils, Kathy L, Choi, Jiyoung, Bin Joo, Young, Bang, So-Young, Lee, Hye-Soon, Bae, Sang-Cheol, Shen, Nan, Qian, Xiaoxia, Tsao, Betty P, Scofield, R Hal, Harley, John B, Webb, Carol F, Wakeland, Edward K, James, Judith A, Nath, Swapan K, Graham, Robert R, and Gaffney, Patrick M
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Lupus ,Autoimmune Disease ,Clinical Research ,Stem Cell Research ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Alleles ,Chromosomes ,Human ,Pair 8 ,Electrophoretic Mobility Shift Assay ,Female ,Genetic Predisposition to Disease ,Haplotypes ,Humans ,Lupus Erythematosus ,Systemic ,Male ,Polymorphism ,Single Nucleotide ,Promoter Regions ,Genetic ,Transcription ,Genetic ,src-Family Kinases ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Efforts to identify lupus-associated causal variants in the FAM167A/BLK locus on 8p21 are hampered by highly associated noncausal variants. In this report, we used a trans-population mapping and sequencing strategy to identify a common variant (rs922483) in the proximal BLK promoter and a tri-allelic variant (rs1382568) in the upstream alternative BLK promoter as putative causal variants for association with systemic lupus erythematosus. The risk allele (T) at rs922483 reduced proximal promoter activity and modulated alternative promoter usage. Allelic differences at rs1382568 resulted in altered promoter activity in B progenitor cell lines. Thus, our results demonstrated that both lupus-associated functional variants contribute to the autoimmune disease association by modulating transcription of BLK in B cells and thus potentially altering immune responses.
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- 2014
74. Insulin Sensitivity and Insulin Clearance Are Heritable and Have Strong Genetic Correlation in Mexican Americans
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Goodarzi, Mark O, Langefeld, Carl D, Xiang, Anny H, Chen, Yii‐Der I, Guo, Xiuqing, Hanley, Anthony JG, Raffel, Leslie J, Kandeel, Fouad, Nadler, Jerry L, Buchanan, Thomas A, Norris, Jill M, Fingerlin, Tasha E, Lorenzo, Carlos, Rewers, Marian J, Haffner, Steven M, Bowden, Donald W, Rich, Stephen S, Bergman, Richard N, Rotter, Jerome I, Watanabe, Richard M, and Wagenknecht, Lynne E
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Clinical Research ,Atherosclerosis ,Genetics ,Diabetes ,Metabolic and endocrine ,Adult ,Aged ,Cohort Studies ,Colorado ,Diabetes Mellitus ,Type 2 ,Female ,Genome-Wide Association Study ,Glucose Clamp Technique ,Glucose Tolerance Test ,Humans ,Insulin ,Insulin Resistance ,Male ,Metabolic Clearance Rate ,Mexican Americans ,Middle Aged ,Pedigree ,Phenotype ,Retrospective Studies ,Texas ,Endocrinology & Metabolism - Abstract
ObjectiveThe GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI).MethodsGUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican-American individuals in 1,346 pedigrees. Insulin sensitivity (SI ), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components.ResultsAcross studies, age, and gender-adjusted heritability of insulin sensitivity (SI , M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to -0.59 for AIRg and MCRI (all P
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- 2014
75. 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 Consortium, on behalf of the Lupus Nephritis–End‐Stage Renal Disease
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Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Kidney Disease ,Genetic Testing ,Clinical Research ,Autoimmune Disease ,Lupus ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Adult ,Black or African American ,Alleles ,Apolipoprotein L1 ,Apolipoproteins ,Disease Progression ,Female ,Genetic Predisposition to Disease ,Genotype ,Humans ,Kidney Failure ,Chronic ,Lipoproteins ,HDL ,Logistic Models ,Lupus Nephritis ,Male ,Middle Aged ,Risk Factors ,White People ,Lupus Nephritis–End‐Stage Renal Disease Consortium ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - 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
76. Deep Resequencing of the 1q22 Locus in Non‐Lobar Intracerebral Hemorrhage.
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Parodi, Livia, Comeau, Mary E., Georgakis, Marios K., Mayerhofer, Ernst, Chung, Jaeyoon, Falcone, Guido J., Malik, Rainer, Demel, Stacie L., Worrall, Bradford B., Koch, Sebastian, Testai, Fernando D., Kittner, Steven J., McCauley, Jacob L., Hall, Christiana E., Mayson, Douglas J., Elkind, Mitchell S.V., James, Michael L., Woo, Daniel, Rosand, Jonathan, and Langefeld, Carl D.
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LACUNAR stroke ,CEREBRAL small vessel diseases ,CEREBRAL hemorrhage ,BASE pairs ,GENOME-wide association studies ,LOCUS (Genetics) - Abstract
Objective: Genome‐wide association studies have identified 1q22 as a susceptibility locus for cerebral small vessel diseases, including non‐lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study, we performed targeted high‐depth sequencing of 1q22 in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown. Methods: A total of 95,000 base pairs spanning 1q22, including SEMA4A, SLC25A44, and PMF1/PMF1‐BGLAP were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non‐lobar) and 1,078 controls. Firth regression and Rare Variant Influential Filtering Tool analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi‐C, chromatin immunoprecipitation followed by sequencing, and chromatin interaction analysis with paired‐end tag databases. Multivariable Mendelian randomization assessed whether alterations in gene‐specific expression relative to regionally co‐expressed genes at 1q22 could be causally related to ICH risk. Results: Common and rare variant analyses prioritized variants in SEMA4A 5′‐UTR and PMF1 intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi‐C data analysis determined that 1q22 is spatially organized in a single chromatin loop, and that the genes therein belong to the same topologically associating domain. Chromatin immunoprecipitation followed by sequencing and chromatin interaction analysis with paired‐end tag data analysis highlighted the presence of long‐range interactions between the SEMA4A‐promoter and PMF1‐enhancer regions prioritized by association testing. Multivariable Mendelian randomization analyses demonstrated that PMF1 overexpression could be causally related to non‐lobar ICH risk. Interpretation: Altered promoter–enhancer interactions leading to PMF1 overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non‐lobar ICH risk at 1q22, offering a potential new target for prevention of ICH and cerebral small vessel disease. ANN NEUROL 2024;95:325–337 [ABSTRACT FROM AUTHOR]
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- 2024
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77. Effects of Intensive Systolic Blood Pressure Control on All-Cause Hospitalizations
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Rocco, Michael V., Comeau, Mary E., Marion, Miranda C., Freedman, Barry I., Hawfield, Amret T., and Langefeld, Carl D.
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- 2020
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78. Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke
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Keene, Keith L., Hyacinth, Hyacinth I., Bis, Joshua C., Kittner, Steven J., Mitchell, Braxton D., Cheng, Yu-Ching, Pare, Guillaume, Chong, Michael, O’Donnell, Martin, Meschia, James F., Chen, Wei-Min, Sale, Michèle M., Rich, Stephen S., Nalls, Mike A., Zonderman, Alan B., Evans, Michele K., Wilson, James G., Correa, Adolfo, Markus, Hugh S., Traylor, Matthew, Lewis, Cathryn M., Carty, Cara L., Reiner, Alexander, Haessler, Jeff, Langefeld, Carl D., Gottesman, Rebecca, Mosley, Thomas H., Woo, Daniel, Yaffe, Kristine, Liu, YongMei, Longstreth, William T., Psaty, Bruce M., Kooperberg, Charles, Lange, Leslie A., Sacco, Ralph, Rundek, Tatjana, Lee, Jin-Moo, Cruchaga, Carlos, Furie, Karen L., Arnett, Donna K., Benavente, Oscar R., Grewal, Raji P., Peddareddygari, Leema Reddy, Dichgans, Martin, Malik, Rainer, Worrall, Bradford B., and Fornage, Myriam
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- 2020
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79. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry
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Monda, Keri L, Chen, Gary K, Taylor, Kira C, Palmer, Cameron, Edwards, Todd L, Lange, Leslie A, Ng, Maggie CY, Adeyemo, Adebowale A, Allison, Matthew A, Bielak, Lawrence F, Chen, Guanjie, Graff, Mariaelisa, Irvin, Marguerite R, Rhie, Suhn K, Li, Guo, Liu, Yongmei, Liu, Youfang, Lu, Yingchang, Nalls, Michael A, Sun, Yan V, Wojczynski, Mary K, Yanek, Lisa R, Aldrich, Melinda C, Ademola, Adeyinka, Amos, Christopher I, Bandera, Elisa V, Bock, Cathryn H, Britton, Angela, Broeckel, Ulrich, Cai, Quiyin, Caporaso, Neil E, Carlson, Chris S, Carpten, John, Casey, Graham, Chen, Wei-Min, Chen, Fang, Chen, Yii-Der I, Chiang, Charleston WK, Coetzee, Gerhard A, Demerath, Ellen, Deming-Halverson, Sandra L, Driver, Ryan W, Dubbert, Patricia, Feitosa, Mary F, Feng, Ye, Freedman, Barry I, Gillanders, Elizabeth M, Gottesman, Omri, Guo, Xiuqing, Haritunians, Talin, Harris, Tamara, Harris, Curtis C, Hennis, Anselm JM, Hernandez, Dena G, McNeill, Lorna H, Howard, Timothy D, Howard, Barbara V, Howard, Virginia J, Johnson, Karen C, Kang, Sun J, Keating, Brendan J, Kolb, Suzanne, Kuller, Lewis H, Kutlar, Abdullah, Langefeld, Carl D, Lettre, Guillaume, Lohman, Kurt, Lotay, Vaneet, Lyon, Helen, Manson, JoAnn E, Maixner, William, Meng, Yan A, Monroe, Kristine R, Morhason-Bello, Imran, Murphy, Adam B, Mychaleckyj, Josyf C, Nadukuru, Rajiv, Nathanson, Katherine L, Nayak, Uma, N'Diaye, Amidou, Nemesure, Barbara, Wu, Suh-Yuh, Leske, M Cristina, Neslund-Dudas, Christine, Neuhouser, Marian, Nyante, Sarah, Ochs-Balcom, Heather, Ogunniyi, Adesola, Ogundiran, Temidayo O, Ojengbede, Oladosu, Olopade, Olufunmilayo I, Palmer, Julie R, Ruiz-Narvaez, Edward A, Palmer, Nicholette D, Press, Michael F, Rampersaud, Evandine, Rasmussen-Torvik, Laura J, Rodriguez-Gil, Jorge L, Salako, Babatunde, and Schadt, Eric E
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Biological Sciences ,Genetics ,Human Genome ,Black or African American ,Body Mass Index ,Case-Control Studies ,Gene Frequency ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Linkage Disequilibrium ,Obesity ,Polymorphism ,Single Nucleotide ,NABEC Consortium ,UKBEC Consortium ,BioBank Japan Project ,AGEN Consortium ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.
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- 2013
80. Variable Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus in Populations with Different African Ancestry
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Ramos, Paula S, Oates, James C, Kamen, Diane L, Williams, Adrienne H, Gaffney, Patrick M, Kelly, Jennifer A, Kaufman, Kenneth M, Kimberly, Robert P, Niewold, Timothy B, Jacob, Chaim O, Tsao, Betty P, Alarcón, Graciela S, Brown, Elizabeth E, Edberg, Jeffrey C, Petri, Michelle A, Ramsey-Goldman, Rosalind, Reveille, John D, Vilá, Luis M, James, Judith A, Guthridge, Joel M, Merrill, Joan T, Boackle, Susan A, Freedman, Barry I, Scofield, R Hal, Stevens, Anne M, Vyse, Timothy J, Criswell, Lindsey A, Moser, Kathy L, Alarcón-Riquelme, Marta E, Langefeld, Carl D, Harley, John B, and Gilkeson, Gary S
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Autoimmune Disease ,Lupus ,Clinical Research ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Adult ,Alleles ,Black People ,Electron Transport Complex I ,Genetic Association Studies ,Genetic Loci ,Genetic Predisposition to Disease ,Genotype ,Glutathione Reductase ,Haplotypes ,Humans ,Lupus Erythematosus ,Systemic ,NADH Dehydrogenase ,Nitric Oxide Synthase Type I ,Polymorphism ,Single Nucleotide ,SYSTEMIC LUPUS ERYTHEMATOSUS ,AFRICAN AMERICANS ,OXYGEN COMPOUNDS ,GENETIC ASSOCIATION STUDIES ,SINGLE-NUCLEOTIDE POLYMORPHISM ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectiveLittle is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry.MethodsA total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations.ResultsThe glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09-1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23-3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44-0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10-1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population.ConclusionThese results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.
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- 2013
81. 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, Group, Bernardo A Pons-Estel on behalf of the Argentine Collaborative, 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, network, Marta E Alarcón-Riquelme on behalf of the BIOLUPUS, Jacob, Chaim O, Sivils, Kathy Moser, Gaffney, Patrick M, Harley, John B, Sawalha, Amr H, and Tsao, Betty P
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Human Genome ,Autoimmune Disease ,Lupus ,Genetics ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Base Sequence ,Chromosome Mapping ,Chromosomes ,Human ,X ,Genetic Predisposition to Disease ,Genotype ,Haplotypes ,Humans ,Interleukin-1 Receptor-Associated Kinases ,Lupus Erythematosus ,Systemic ,Methyl-CpG-Binding Protein 2 ,Molecular Sequence Data ,Polymorphism ,Single Nucleotide ,Racial Groups ,Real-Time Polymerase Chain Reaction ,Risk Factors ,Argentine Collaborative Group ,BIOLUPUS network ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - 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
82. Unraveling Multiple MHC Gene Associations with Systemic Lupus Erythematosus: Model Choice Indicates a Role for HLA Alleles and Non-HLA Genes in Europeans
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Morris, David L, Taylor, Kimberly E, Fernando, Michelle MA, Nititham, Joanne, Alarcón-Riquelme, Marta E, Barcellos, Lisa F, Behrens, Timothy W, Cotsapas, Chris, Gaffney, Patrick M, Graham, Robert R, Pons-Estel, Bernardo A, Gregersen, Peter K, Harley, John B, Hauser, Stephen L, Hom, Geoffrey, Network, International MHC and Autoimmunity Genetics, Langefeld, Carl D, Noble, Janelle A, Rioux, John D, Seldin, Michael F, Consortium, Systemic Lupus Erythematosus Genetics, Criswell, Lindsey A, and Vyse, Timothy J
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Immunology ,Clinical Research ,Autoimmune Disease ,Lupus ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Alleles ,Gene Expression Profiling ,Genetic Predisposition to Disease ,Genotype ,HLA Antigens ,HLA-B Antigens ,HLA-C Antigens ,HLA-DQ alpha-Chains ,HLA-DRB1 Chains ,Haplotypes ,Humans ,Lupus Erythematosus ,Systemic ,Major Histocompatibility Complex ,Polymorphism ,Single Nucleotide ,White People ,International MHC and Autoimmunity Genetics Network ,Systemic Lupus Erythematosus Genetics Consortium ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
We have performed a meta-analysis of the major-histocompatibility-complex (MHC) region in systemic lupus erythematosus (SLE) to determine the association with both SNPs and classical human-leukocyte-antigen (HLA) alleles. More specifically, we combined results from six studies and well-known out-of-study control data sets, providing us with 3,701 independent SLE cases and 12,110 independent controls of European ancestry. This study used genotypes for 7,199 SNPs within the MHC region and for classical HLA alleles (typed and imputed). Our results from conditional analysis and model choice with the use of the Bayesian information criterion show that the best model for SLE association includes both classical loci (HLA-DRB1(∗)03:01, HLA-DRB1(∗)08:01, and HLA-DQA1(∗)01:02) and two SNPs, rs8192591 (in class III and upstream of NOTCH4) and rs2246618 (MICB in class I). Our approach was to perform a stepwise search from multiple baseline models deduced from a priori evidence on HLA-DRB1 lupus-associated alleles, a stepwise regression on SNPs alone, and a stepwise regression on HLA alleles. With this approach, we were able to identify a model that was an overwhelmingly better fit to the data than one identified by simple stepwise regression either on SNPs alone (Bayes factor [BF] > 50) or on classical HLA alleles alone (BF > 1,000).
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- 2012
83. 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, Networks, BIOLUPUS and GENLES, Alarcón, Graciela S, Anaya, Juan‐Manuel, Bae, Sang‐Cheol, Kim, Jae‐Hoon, Bin Joo, Young, 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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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Clinical Research ,Human Genome ,Lupus ,Autoimmune Disease ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Adaptor Proteins ,Signal Transducing ,Black or African American ,Asian ,B-Lymphocytes ,Cell Line ,Transformed ,DNA-Binding Proteins ,Female ,Genetic Markers ,Genetic Predisposition to Disease ,Haplotypes ,Hispanic or Latino ,Humans ,Intracellular Signaling Peptides and Proteins ,Lupus Erythematosus ,Systemic ,Male ,Neoplasm Proteins ,Polymorphism ,Single Nucleotide ,Risk Factors ,United States ,White People ,BIOLUPUS and GENLES Networks ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - 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.
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- 2012
84. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian–European populations
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Sánchez, Elena, Rasmussen, Astrid, Riba, Laura, Acevedo‐Vasquez, Eduardo, Kelly, Jennifer A, Langefeld, Carl D, Williams, Adrianne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, La Torre, Ignacio García‐De, Maradiaga‐Ceceña, Marco A, Cardiel, Mario H, Esquivel‐Valerio, Jorge A, Rodriguez‐Amado, Jacqueline, Moctezuma, José Francisco, Miranda, Pedro, Perandones, Carlos E, Castel, Cecilia, Laborde, Hugo A, Alba, Paula, Musuruana, Jorge L, Goecke, I Annelise, Anaya, Juan‐Manuel, Kaufman, Kenneth M, Adler, Adam, Glenn, Stuart B, Brown, Elizabeth E, Alarcón, Graciela S, Kimberly, Robert P, Edberg, Jeffrey C, Vilá, Luis M, Criswell, Lindsey A, Gilkeson, Gary S, Niewold, Timothy B, Martín, Javier, Vyse, Timothy J, Boackle, Susan A, Ramsey‐Goldman, Rosalind, Scofield, R Hal, Petri, Michelle, Merrill, Joan T, Reveille, John D, Tsao, Betty P, Orozco, Lorena, Baca, Vicente, Moser, Kathy L, Gaffney, Patrick M, James, Judith A, Harley, John B, Tusié‐Luna, Teresa, Pons‐Estel, Bernardo A, Jacob, Chaim O, and Alarcón‐Riquelme, Marta E
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Biological Sciences ,Biomedical and Clinical Sciences ,Health Sciences ,Genetics ,Autoimmune Disease ,Clinical Research ,Lupus ,Kidney Disease ,American Indian or Alaska Native ,Inflammatory and immune system ,Adolescent ,Adult ,Child ,Female ,Genetic Predisposition to Disease ,Genotype ,Humans ,Indians ,North American ,Indians ,South American ,Lupus Erythematosus ,Systemic ,Lupus Nephritis ,Male ,Middle Aged ,Morbidity ,Prevalence ,Risk Factors ,Socioeconomic Factors ,White People ,Young Adult ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveAmerican Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients.MethodsA total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).ResultsThe average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement.ConclusionIn general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.
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- 2012
85. Minority Patients are Less Likely to Undergo Withdrawal of Care After Spontaneous Intracerebral Hemorrhage
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Ormseth, Cora H., Falcone, Guido J., Jasak, Sara D., Mampre, David M., Leasure, Audrey C., Miyares, Laura C., Hwang, David Y., James, Michael L., Testai, Fernando D., Becker, Kyra J., Tirschwell, David L., Langefeld, Carl D., Woo, Daniel, and Sheth, Kevin N.
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- 2018
- Full Text
- View/download PDF
86. Evaluation of TRAF6 in a large multiancestral lupus cohort
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Namjou, Bahram, Choi, Chan‐Bum, Harley, Isaac TW, Alarcón‐Riquelme, Marta E, Network, BIOLUPUS, Kelly, Jennifer A, Glenn, Stuart B, Ojwang, Joshua O, Adler, Adam, Kim, Kwangwoo, 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, Network, Genoma en Lupus, 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, and Bae, Sang‐Cheol
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Epidemiology ,Health Sciences ,Lupus ,Clinical Research ,Arthritis ,Autoimmune Disease ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Alleles ,Case-Control Studies ,Cohort Studies ,Female ,Gene Frequency ,Genetic Association Studies ,Genetic Predisposition to Disease ,Genotype ,Haplotypes ,Humans ,Lupus Erythematosus ,Systemic ,Male ,Polymorphism ,Single Nucleotide ,TNF Receptor-Associated Factor 6 ,BIOLUPUS Network ,Genoma en Lupus Network ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveSystemic 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.MethodsFifteen 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.ResultsEvidence 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.ConclusionOur 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.
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- 2012
87. A genome-wide association search for type 2 diabetes genes in African Americans.
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Palmer, Nicholette D, McDonough, Caitrin W, Hicks, Pamela J, Roh, Bong H, Wing, Maria R, An, S Sandy, Hester, Jessica M, Cooke, Jessica N, Bostrom, Meredith A, Rudock, Megan E, Talbert, Matthew E, Lewis, Joshua P, DIAGRAM Consortium, MAGIC Investigators, Ferrara, Assiamira, Lu, Lingyi, Ziegler, Julie T, Sale, Michele M, Divers, Jasmin, Shriner, Daniel, Adeyemo, Adebowale, Rotimi, Charles N, Ng, Maggie CY, Langefeld, Carl D, Freedman, Barry I, Bowden, Donald W, Voight, Benjamin F, Scott, Laura J, Steinthorsdottir, Valgerdur, Morris, Andrew P, Dina, Christian, Welch, Ryan P, Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S, Thorleifsson, Gudmar, McCulloch, Laura J, Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J, Raychaudhuri, Soumya, McCarroll, Steve A, Langenberg, Claudia, Hofmann, Oliver M, Dupuis, Josée, Qi, Lu, Segrè, Ayellet V, van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J, Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L, Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P, Charpentier, Guillaume, Chines, Peter S, Cornelis, Marilyn, Couper, David J, Crawford, Gabe, Doney, Alex SF, Elliott, Katherine S, Elliott, Amanda L, Erdos, Michael R, Fox, Caroline S, Franklin, Christopher S, Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J, Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U, Johnson, Paul RV, Jørgensen, Torben, Kao, Wen HL, Klopp, Norman, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M, Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, and Midthjell, Kristian
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DIAGRAM Consortium ,MAGIC Investigators ,Humans ,Diabetes Mellitus ,Type 2 ,Genetic Predisposition to Disease ,Case-Control Studies ,Cohort Studies ,Genotype ,Polymorphism ,Single Nucleotide ,Adult ,Aged ,Middle Aged ,African Americans ,Female ,Male ,Meta-Analysis as Topic ,Validation Studies as Topic ,Genome-Wide Association Study ,Diabetes Mellitus ,Type 2 ,Polymorphism ,Single Nucleotide ,General Science & Technology - Abstract
African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P
- Published
- 2012
88. Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant
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Wang, Qiang, Martínez-Bonet, Marta, Kim, Taehyeung, Sparks, Jeffrey A., Ishigaki, Kazuyoshi, Chen, Xiaoting, Sudman, Marc, Aguiar, Vitor, Sim, Sangwan, Hernandez, Marcos Chiñas, Chiu, Darren J., Wactor, Alexandra, Wauford, Brian, Marion, Miranda C., Gutierrez-Arcelus, Maria, Bowes, John, Eyre, Stephen, Nordal, Ellen, Prahalad, Sampath, Rygg, Marite, Videm, Vibeke, Raychaudhuri, Soumya, Weirauch, Matthew T., Langefeld, Carl D., Thompson, Susan D., and Nigrovic, Peter A.
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- 2024
- Full Text
- View/download PDF
89. A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap.
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Ramos, Paula S, Criswell, Lindsey A, Moser, Kathy L, Comeau, Mary E, Williams, Adrienne H, Pajewski, Nicholas M, Chung, Sharon A, Graham, Robert R, Zidovetzki, Raphael, Kelly, Jennifer A, Kaufman, Kenneth M, Jacob, Chaim O, Vyse, Timothy J, Tsao, Betty P, Kimberly, Robert P, Gaffney, Patrick M, Alarcón-Riquelme, Marta E, Harley, John B, Langefeld, Carl D, and International Consortium on the Genetics of Systemic Erythematosus
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International Consortium on the Genetics of Systemic Erythematosus ,Humans ,Arthritis ,Rheumatoid ,Colitis ,Ulcerative ,Crohn Disease ,Lupus Erythematosus ,Systemic ,Diabetes Mellitus ,Type 1 ,Autoimmune Diseases ,Genetic Predisposition to Disease ,Receptors ,Interleukin ,Case-Control Studies ,Cohort Studies ,Polymorphism ,Single Nucleotide ,European Continental Ancestry Group ,OX40 Ligand ,Interleukin-2 Receptor alpha Subunit ,Genome-Wide Association Study ,Genetic Pleiotropy ,V-Set Domain-Containing T-Cell Activation Inhibitor 1 ,Arthritis ,Rheumatoid ,Colitis ,Ulcerative ,Lupus Erythematosus ,Systemic ,Diabetes Mellitus ,Type 1 ,Receptors ,Interleukin ,Polymorphism ,Single Nucleotide ,Genetics ,Developmental Biology - Abstract
In spite of the well-known clustering of multiple autoimmune disorders in families, analyses of specific shared genes and polymorphisms between systemic lupus erythematosus (SLE) and other autoimmune diseases (ADs) have been limited. Therefore, we comprehensively tested autoimmune variants for association with SLE, aiming to identify pleiotropic genetic associations between these diseases. We compiled a list of 446 non-Major Histocompatibility Complex (MHC) variants identified in genome-wide association studies (GWAS) of populations of European ancestry across 17 ADs. We then tested these variants in our combined Caucasian SLE cohorts of 1,500 cases and 5,706 controls. We tested a subset of these polymorphisms in an independent Caucasian replication cohort of 2,085 SLE cases and 2,854 controls, allowing the computation of a meta-analysis between all cohorts. We have uncovered novel shared SLE loci that passed multiple comparisons adjustment, including the VTCN1 (rs12046117, P = 2.02×10(-06)) region. We observed that the loci shared among the most ADs include IL23R, OLIG3/TNFAIP3, and IL2RA. Given the lack of a universal autoimmune risk locus outside of the MHC and variable specificities for different diseases, our data suggests partial pleiotropy among ADs. Hierarchical clustering of ADs suggested that the most genetically related ADs appear to be type 1 diabetes with rheumatoid arthritis and Crohn's disease with ulcerative colitis. These findings support a relatively distinct genetic susceptibility for SLE. For many of the shared GWAS autoimmune loci, we found no evidence for association with SLE, including IL23R. Also, several established SLE loci are apparently not associated with other ADs, including the ITGAM-ITGAX and TNFSF4 regions. This study represents the most comprehensive evaluation of shared autoimmune loci to date, supports a relatively distinct non-MHC genetic susceptibility for SLE, provides further evidence for previously and newly identified shared genes in SLE, and highlights the value of studies of potentially pleiotropic genes in autoimmune diseases.
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- 2011
90. Genomewide linkage scan for diabetic renal failure and albuminuria: the FIND study.
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Igo, Robert P, Jr, Iyengar, Sudha K, Nicholas, Susanne B, Goddard, Katrina A B, Langefeld, Carl D, Hanson, Robert L, Duggirala, Ravindranath, Divers, Jasmin, Abboud, Hanna, Adler, Sharon G, Arar, Nedal H, Horvath, Amanda, Elston, Robert C, Bowden, Donald W, Guo, Xiuqing, Ipp, Eli, Kao, W H Linda, Kimmel, Paul L, Knowler, William C, Meoni, Lucy A, Molineros, Julio, Nelson, Robert G, Pahl, Madeline V, Parekh, Rulan S, Rasooly, Rebekah S, Schelling, Jeffrey R, Shah, Vallabh O, Smith, Michael W, Winkler, Cheryl A, Zager, Philip G, Sedor, John R, and Freedman, Barry I
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Aged ,Albuminuria: genetics ,metabolism ,Chromosome Mapping ,Diabetic Nephropathies: genetics ,metabolism ,Ethnic Groups ,Female ,Genetic Linkage ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Male ,Middle Aged ,Pedigree ,Polymorphism ,Single Nucleotide ,Renal Insufficiency: genetics ,metabolism ,Risk ,Time Factors - Abstract
Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals.A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations.Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10(-5), LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies.These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN.
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- 2011
91. Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.
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Chung, Sharon A, Taylor, Kimberly E, Graham, Robert R, Nititham, Joanne, Lee, Annette T, Ortmann, Ward A, Jacob, Chaim O, Alarcón-Riquelme, Marta E, Tsao, Betty P, Harley, John B, Gaffney, Patrick M, Moser, Kathy L, SLEGEN, Petri, Michelle, Demirci, F Yesim, Kamboh, M Ilyas, Manzi, Susan, Gregersen, Peter K, Langefeld, Carl D, Behrens, Timothy W, and Criswell, Lindsey A
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SLEGEN ,Humans ,Lupus Erythematosus ,Systemic ,Genetic Predisposition to Disease ,DNA ,Autoantibodies ,Case-Control Studies ,Major Histocompatibility Complex ,Polymorphism ,Single Nucleotide ,STAT4 Transcription Factor ,Interferon Regulatory Factors ,Genetic Variation ,Genome-Wide Association Study ,CD11b Antigen ,Lupus Erythematosus ,Systemic ,Polymorphism ,Single Nucleotide ,Antigens ,CD11b ,Genetics ,Developmental Biology - Abstract
Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti-dsDNA autoantibody production, a SLE-related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti-dsDNA autoantibody positive (anti-dsDNA +, n = 811) and anti-dsDNA autoantibody negative (anti-dsDNA -, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE. Far fewer and weaker associations were observed for anti-dsDNA - SLE. For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20) compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04), with p(heterogeneity)
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- 2011
92. Identification of influential rare variants in aggregate testing using random forest importance measures
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Blumhagen, Rachel Z., primary, Schwartz, David A., additional, Langefeld, Carl D., additional, and Fingerlin, Tasha E., additional
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- 2023
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93. Variability in the Use of Platelet Transfusion in Patients with Intracerebral Hemorrhage: Observations from the Ethnic/Racial Variations of Intracerebral Hemorrhage Study
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Guerrero, Waldo R., Gonzales, Nicole R., Sekar, Padmini, Kawano-Castillo, Jorge, Moomaw, Charles J., Worrall, Bradford B., Langefeld, Carl D., Martini, Sharyl R., Flaherty, Matthew L., Sheth, Kevin N., Osborne, Jennifer, and Woo, Daniel
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- 2017
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94. Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage
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Biffi, Alessandro, Urday, Sebastian, Kubiszewski, Patryk, Gilkerson, Lee, Sekar, Padmini, Rodriguez-Torres, Axana, Bettin, Margaret, Charidimou, Andreas, Pasi, Marco, Kourkoulis, Christina, Schwab, Kristin, DiPucchio, Zora, Behymer, Tyler, Osborne, Jennifer, Morgan, Misty, Moomaw, Charles J., James, Michael L., Greenberg, Steven M., Viswanathan, Anand, Gurol, M. Edip, Worrall, Bradford B., Testai, Fernando D., McCauley, Jacob L., Falcone, Guido J., Langefeld, Carl D., Anderson, Christopher D., Kamel, Hooman, Woo, Daniel, Sheth, Kevin N., and Rosand, Jonathan
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- 2020
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95. Type 2 Diabetes: Evidence for Linkage on Chromosome 20 in 716 Finnish Affected Sib Pairs
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Ghosh, Soumitra, Watanabe, Richard M., Hauser, Elizabeth R., Valle, Timo, Magnuson, Victoria L., Erdos, Michael R., Langefeld, Carl D., Balow,, James, Ally, Delphine S., Kohtamaki, Kimmo, Chines, Peter, Birznieks, Gunther, Kaleta, Hong-Shi, Musick, Anjene, Te, Catherine, Tannenbaum, Joyce, Eldridge, William, Shapiro, Shane, Martin, Colin, Witt, Alyson, So, Alistair, Chang, Jennie, Shurtleff, Ben, Porter, Rachel, Kudelko, Kristina, Unni, Arun, Segal, Leonid, Sharaf, Ravi, Blaschak-Harvan, Jillian, Eriksson, Johan, Tenkula, Tuula, Vidgren, Gabriele, Ehnholm, Christian, Tuomilehto-Wolf, Eva, Hagopian, William, Buchanan, Thomas A., Tuomilehto, Jaakko, Bergman, Richard N., Collins, Francis S., and Boehnke, Michael
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- 1999
96. Acis-regulatory element regulatesERAP2expression through autoimmune disease risk SNPs
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Venema, Wouter J., primary, Hiddingh, Sanne, additional, van Loosdregt, Jorg, additional, Bowes, John, additional, Balliu, Brunilda, additional, de Boer, Joke H., additional, Norel, Jeanette Ossewaarde-van, additional, Thompson, Susan. D., additional, Langefeld, Carl D., additional, van der Veken, Lars T., additional, Sofiadis, Konstantinos, additional, Krijger, Peter H.L., additional, de Laat, Wouter, additional, and Kuiper, Jonas J.W., additional
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- 2023
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97. Admixture mapping of serum vitamin D and parathyroid hormone concentrations in the African American—Diabetes Heart Study
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Palmer, Nicholette D., Divers, Jasmin, Lu, Lingyi, Register, Thomas C., Carr, J. Jeffrey, Hicks, Pamela J., Smith, S. Carrie, Xu, Jianzhao, Judd, Suzanne E., Irvin, Marguerite R., Gutierrez, Orlando M., Bowden, Donald W., Wagenknecht, Lynne E., Langefeld, Carl D., and Freedman, Barry I.
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- 2016
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98. Analysis of advanced glycation end products in the DHS Mind Study
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Adams, Jeremy N., Martelle, Susan E., Raffield, Laura M., Freedman, Barry I., Langefeld, Carl D., Hsu, Fang-Chi, Maldjian, Joseph A., Williamson, Jeff D., Hugenschmidt, Christina E., Carr, J. Jeffery, Cox, Amanda J., and Bowden, Donald W.
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- 2016
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99. Erratum: Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium
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Fernández-Rhodes, Lindsay, Graff, Mariaelisa, Buchanan, Victoria L, Justice, Anne E, Highland, Heather M, Guo, Xiuqing, Zhu, Wanying, Chen, Hung-Hsin, Young, Kristin L, Adhikari, Kaustubh, Palmer, Nicholette D, Below, Jennifer E, Bradfield, Jonathan, Pereira, Alexandre C, Glover, LáShauntá, Kim, Daeeun, Lilly, Adam G, Shrestha, Poojan, Thomas, Alvin G, Zhang, Xinruo, Chen, Minhui, Chiang, Charleston WK, Pulit, Sara, Horimoto, Andrea, Krieger, Jose E, Guindo-Martínez, Marta, Preuss, Michael, Schumann, Claudia, Smit, Roelof AJ, Torres-Mejía, Gabriela, Acuña-Alonzo, Victor, Bedoya, Gabriel, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, González-José, Rolando, Poletti, Giovanni, Rothhammer, Francisco, Hakonarson, Hakon, Igo, Robert, Adler, Sharon G, Iyengar, Sudha K, Nicholas, Susanne B, Gogarten, Stephanie M, Isasi, Carmen R, Papnicolaou, George, Stilp, Adrienne M, Qi, Qibin, Kho, Minjung, Smith, Jennifer A, Langefeld, Carl D, Wagenknecht, Lynne, Mckean-Cowdin, Roberta, Gao, Xiaoyi Raymond, Nousome, Darryl, Conti, David V, Feng, Ye, Allison, Matthew A, Arzumanyan, Zorayr, Buchanan, Thomas A, Chen, Yii-Der Ida, Genter, Pauline M, Goodarzi, Mark O, Hai, Yang, Hsueh, Willa, Ipp, Eli, Kandeel, Fouad R, Lam, Kelvin, Li, Xiaohui, Nadler, Jerry L, Raffel, Leslie J, Roll, Kathryn, Sandow, Kevin, Tan, Jingyi, Taylor, Kent D, Xiang, Anny H, Yao, Jie, Audirac-Chalifour, Astride, Peralta Romero, Jose de Jesus, Hartwig, Fernando, Horta, Bernando, Blangero, John, Curran, Joanne E, Duggirala, Ravindranath, Lehman, Donna E, Puppala, Sobha, Fejerman, Laura, John, Esther M, Aguilar-Salinas, Carlos, Burtt, Noël P, Florez, Jose C, García-Ortíz, Humberto, González-Villalpando, Clicerio, Mercader, Josep, Orozco, Lorena, Tusié-Luna, Teresa, Blanco, Estela, Gahagan, Sheila, Cox, Nancy J, and Hanis, Craig
- Abstract
[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].
- Published
- 2023
100. HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis
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British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group, Childhood Arthritis Prospective Study (CAPS) Group, Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators, Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group, Biologically Based Outcome Predictors in JIA (BBOP) Group, International Childhood Arthritis Genetics (INCHARGE) Consortium, Ombrello, Michael J., Remmers, Elaine F., Tachmazidou, Ioanna, Grom, Alexei, Foell, Dirk, Haas, Johannes-Peter, Martini, Alberto, Gattorno, Marco, Özen, Seza, Prahalad, Sampath, Zeft, Andrew S., Bohnsack, John F., Mellins, Elizabeth D., Ilowite, Norman T., Russo, Ricardo, Len, Claudio, Hilario, Maria Odete E., Oliveira, Sheila, Yeung, Rae S.M., Rosenberg, Alan, Wedderburn, Lucy R., Anton, Jordi, Schwarz, Tobias, Hinks, Anne, Bilginer, Yelda, Park, Jane, Cobb, Joanna, Satorius, Colleen L., Han, Buhm, Baskin, Elizabeth, Signa, Sara, Duerr, Richard H., Achkar, J. P., Kamboh, M. Ilyas, Kaufman, Kenneth M., Kottyan, Leah C., Pinto, Dalila, Scherer, Stephen W., Alarcón-Riquelme, Marta E., Docampo, Elisa, Estivill, Xavier, Gül, Ahmet, de Bakker, Paul I. W., Raychaudhuri, Soumya, Langefeld, Carl D., Thompson, Susan, Zeggini, Eleftheria, Thomson, Wendy, Kastner, Daniel L., and Woo, Patricia
- Published
- 2015
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