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Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits.
Liu, Lili; Khan, Atlas; Sanchez-Rodriguez, Elena; Zanoni, Francesca; Li, Yifu; Steers, Nicholas; Balderes, Olivia; Zhang, Junying; Krithivasan, Priya; LeDesma, Robert A; Fischman, Clara; Hebbring, Scott J; Harley, John B; Moncrieffe, Halima; Kottyan, Leah C; Namjou-Khales, Bahram; Walunas, Theresa L; Knevel, Rachel; Raychaudhuri, Soumya; Karlson, Elizabeth W; Denny, Joshua C; Stanaway, Ian B; Crosslin, David; Rauen, Thomas; Floege, Jürgen; Eitner, Frank; Moldoveanu, Zina; Reily, Colin; Knoppova, Barbora; Hall, Stacy; Sheff, Justin T; Julian, Bruce A; Wyatt, Robert J; Suzuki, Hitoshi; Xie, Jingyuan; Chen, Nan; Zhou, Xujie; Zhang, Hong; Hammarström, Lennart; Viktorin, Alexander; Magnusson, Patrik K E; Shang, Ning; Hripcsak, George; Weng, Chunhua; Rundek, Tatjana; Elkind, Mitchell S V; Oelsner, Elizabeth C; Barr, R Graham; Ionita-Laza, Iuliana; Novak, Jan.
Afiliación
  • Liu L; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Khan A; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Sanchez-Rodriguez E; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Zanoni F; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Li Y; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Steers N; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Balderes O; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Zhang J; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Krithivasan P; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • LeDesma RA; Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
  • Fischman C; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Hebbring SJ; Center for Human Genetics, Marshfield Clinic Research Institute, Marshfield, WI, USA.
  • Harley JB; Center of Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
  • Moncrieffe H; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Kottyan LC; US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
  • Namjou-Khales B; Center of Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
  • Walunas TL; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Knevel R; Center of Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
  • Raychaudhuri S; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Karlson EW; Center of Autoimmune Genomics and Etiology, Cincinnati Children's Hospital, Cincinnati, OH, USA.
  • Denny JC; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Stanaway IB; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Crosslin D; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Rauen T; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Floege J; Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Eitner F; Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Moldoveanu Z; Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Reily C; Department of Biomedical Informatics and Medical Education, School of Medicine, University of Washington, Seattle, WA, USA.
  • Knoppova B; Department of Nephrology, RWTH University of Aachen, Aachen, Germany.
  • Hall S; Department of Nephrology, RWTH University of Aachen, Aachen, Germany.
  • Sheff JT; Department of Nephrology, RWTH University of Aachen, Aachen, Germany.
  • Julian BA; Kidney Diseases Research, Bayer Pharma AG, Wuppertal, Germany.
  • Wyatt RJ; Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Suzuki H; Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Xie J; Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Chen N; Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Zhou X; Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Zhang H; Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Hammarström L; Division of Pediatric Nephrology, University of Tennessee Health Sciences Center, Memphis, TN, USA.
  • Viktorin A; Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
  • Magnusson PKE; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Shang N; Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Hripcsak G; Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
  • Weng C; Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
  • Rundek T; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
  • Elkind MSV; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Oelsner EC; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Barr RG; Department of Biomedical Informatics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Ionita-Laza I; Department of Biomedical Informatics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Novak J; Department of Biomedical Informatics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
Nat Commun ; 13(1): 6859, 2022 11 11.
Article en En | MEDLINE | ID: mdl-36369178
ABSTRACT
Immunoglobulin A (IgA) mediates mucosal responses to food antigens and the intestinal microbiome and is involved in susceptibility to mucosal pathogens, celiac disease, inflammatory bowel disease, and IgA nephropathy. We performed a genome-wide association study of serum IgA levels in 41,263 individuals of diverse ancestries and identified 20 genome-wide significant loci, including 9 known and 11 novel loci. Co-localization analyses with expression QTLs prioritized candidate genes for 14 of 20 significant loci. Most loci encoded genes that produced immune defects and IgA abnormalities when genetically manipulated in mice. We also observed positive genetic correlations of serum IgA levels with IgA nephropathy, type 2 diabetes, and body mass index, and negative correlations with celiac disease, inflammatory bowel disease, and several infections. Mendelian randomization supported elevated serum IgA as a causal factor in IgA nephropathy. African ancestry was consistently associated with higher serum IgA levels and greater frequency of IgA-increasing alleles compared to other ancestries. Our findings provide novel insights into the genetic regulation of IgA levels and its potential role in human disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Enfermedad Celíaca / Diabetes Mellitus Tipo 2 / Glomerulonefritis por IGA Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Enfermedad Celíaca / Diabetes Mellitus Tipo 2 / Glomerulonefritis por IGA Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos