guest ::
| Home > Articles > Published articles > The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis |
| Home > Articles > Published articles > The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis |
(Columbia University) (Istituto di Ricerca Genetica e Biomedica) (Columbia University) (Columbia University) (Columbia University) (Columbia University) (Columbia University) (Columbia University) (University of Michigan School of Medicine) (Institute of Biochemistry and Biophysics) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Bern University Hospital) (Marmara University) (Istanbul University) (University of Messina) (Charles University) (University of Verona) (Seoul National University) (Juntendo University) (University of Torino) (University College London) (University College London) (Icahn School of Medicine at Mount Sinai) (University of Freiburg) (University of Freiburg) (University of Washington) (University of Michigan) (Institut National de la Santé et de la Recherche Médicale) (Radboud University Medical Center) (Istituto di Ricerca Genetica e Biomedica) (Peking-Tsinghua Center for Life Sciences) (Columbia University) (University College London) (Columbia University)| Date: | 2020 |
| Abstract: | Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1. 25, P = 3. 4 × 10 −12) and IRF4 (rs9405192, OR = 1. 29, P = 1. 4 × 10 −14), fine-map the PLA2R1 locus (rs17831251, OR = 2. 25, P = 4. 7 × 10 −103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3. 81, P = 2. 0 × 10 −49), DQA1*0501 in Europeans (OR = 2. 88, P = 5. 7 × 10 −93), and DRB1*0301 in both ethnicities (OR = 3. 50, P = 9. 2 × 10 −23 and OR = 3. 39, P = 5. 2 × 10 −82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk. Membranous nephropathy (MN) is a rare autoimmune disease of podocyte-directed antibodies, such as anti-phospholipase A2 receptor. Here, the authors report a genome-wide association study for MN and identify two previously unreported loci encompassing the NFKB1 and IRF4 genes and additional ancestry-specific effects. |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Altres ; recerca ; Versió publicada |
| Subject: | Genome-wide association studies ; Autoimmunity ; Immunogenetics ; Membranous nephropathy |
| Published in: | Nature communications, Vol. 11 (march 2020) , ISSN 2041-1723 |
