The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis
Articolo
Data di Pubblicazione:
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.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
genetics, membranous nephropahty, GWAS, HLA
Elenco autori:
Xie, Jingyuan; Liu, Lili; Mladkova, Nikol; Li, Yifu; Ren, Hong; Wang, Weiming; Cui, Zhao; Lin, Li; Hu, Xiaofan; Yu, Xialian; Xu, Jing; Liu, Gang; Caliskan, Yasar; Sidore, Carlo; Balderes, Olivia; Rosen, Raphael J; Bodria, Monica; Zanoni, Francesca; Zhang, Jun Y; Krithivasan, Priya; Mehl, Karla; Marasa, Maddalena; Khan, Atlas; Ozay, Fatih; Canetta, Pietro A; Bomback, Andrew S; Appel, Gerald B; Sanna-Cherchi, Simone; Sampson, Matthew G; Mariani, Laura H; Perkowska-Ptasinska, Agnieszka; Durlik, Magdalena; Mucha, Krzysztof; Moszczuk, Barbara; Foroncewicz, Bartosz; Pączek, Leszek; Habura, Ireneusz; Ars, Elisabet; Ballarin, Jose; Mani, Laila-Yasmin; Vogt, Bruno; Ozturk, Savas; Yildiz, Abdülmecit; Seyahi, Nurhan; Arikan, Hakki; Koc, Mehmet; Basturk, Taner; Karahan, Gonca; Akgul, Sebahat Usta; Sever, Mehmet Sukru; Zhang, Dan; Santoro, Domenico; Bonomini, Mario; Londrino, Francesco; Gesualdo, Loreto; Reiterova, Jana; Tesar, Vladimir; Izzi, Claudia; Savoldi, Silvana; Spotti, Donatella; Marcantoni, Carmelita; Messa, Piergiorgio; Galliani, Marco; Roccatello, Dario; Granata, Simona; Zaza, Gianluigi; Lugani, Francesca; Ghiggeri, GianMarco; Pisani, Isabella; Allegri, Landino; Sprangers, Ben; Park, Jin-Ho; Cho, BeLong; Kim, Yon Su; Kim, Dong Ki; Suzuki, Hitoshi; Amoroso, Antonio; Cattran, Daniel C; Fervenza, Fernando C; Pani, Antonello; Hamilton, Patrick; Harris, Shelly; Gupta, Sanjana; Cheshire, Chris; Dufek, Stephanie; Issler, Naomi; Pepper, Ruth J; Connolly, John; Powis, Stephen; Bockenhauer, Detlef; Stanescu, Horia C; Ashman, Neil; Loos, Ruth J F; Kenny, Eimear E; Wuttke, Matthias; Eckardt, Kai-Uwe; Köttgen, Anna; Hofstra, Julia M; Coenen, Marieke J H; Kiemeney, Lambertus A; Akilesh, Shreeram; Kretzler, Matthias; Beck, Lawrence H; Stengel, Benedicte; Debiec, Hanna; Ronco, Pierre; Wetzels, Jack F M; Zoledziewska, Magdalena; Cucca, Francesco; Ionita-Laza, Iuliana; Lee, Hajeong; Hoxha, Elion; Stahl, Rolf A K; Brenchley, Paul; Scolari, Francesco; Zhao, Ming-Hui; Gharavi, Ali G; Kleta, Robert; Chen, Nan; Kiryluk, Krzysztof
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