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:
1.1 Articolo in rivista
Elenco autori:
Xie, J; Liu, L; Mladkova, N; Li, Y; Ren, H; Wang, W; Cui, Z; Lin, L; Hu, X; Yu, X; Xu, J; Liu, G; Caliskan, Y; Sidore, C; Balderes, O; Rosen, Rj; Bodria, M; Zanoni, F; Zhang, Jy; Krithivasan, P; Mehl, K; Marasa, M; Khan, A; Ozay, F; Canetta, Pa; Bomback, As; Appel, Gb; Sanna-Cherchi, S; Sampson, Mg; Mariani, Lh; Perkowska-Ptasinska, A; Durlik, M; Mucha, K; Moszczuk, B; Foroncewicz, B; Pączek, L; Habura, I; Ars, E; Ballarin, J; Mani, Ly; Vogt, B; Ozturk, S; Yildiz, A; Seyahi, N; Arikan, H; Koc, M; Basturk, T; Karahan, G; Akgul, Su; Sever, Ms; Zhang, D; Santoro, D; Bonomini, M; Londrino, F; Gesualdo, L; Reiterova, J; Tesar, V; Izzi, C; Savoldi, S; Spotti, D; Marcantoni, C; Messa, P; Galliani, M; Roccatello, D; Granata, S; Zaza, G; Lugani, F; Ghiggeri, G; Pisani, I; Allegri, L; Sprangers, B; Park, Jh; Cho, B; Kim, Ys; Kim, Dk; Suzuki, H; Amoroso, A; Cattran, Dc; Fervenza, Fc; Pani, A; Hamilton, P; Harris, S; Gupta, S; Cheshire, C; Dufek, S; Issler, N; Pepper, Rj; Connolly, J; Powis, S; Bockenhauer, D; Stanescu, Hc; Ashman, N; Loos, Rjf; Kenny, Ee; Wuttke, M; Eckardt, Ku; Köttgen, A; Hofstra, Jm; Coenen, Mjh; Kiemeney, La; Akilesh, S; Kretzler, M; Beck, Lh; Stengel, B; Debiec, H; Ronco, P; Wetzels, Jfm; Zoledziewska, M; Cucca, F; Ionita-Laza, I; Lee, H; Hoxha, E; Stahl, Rak; Brenchley, P; Scolari, F; Zhao, Mh; Gharavi, Ag; Kleta, R; Chen, N; Kiryluk, K.
Link alla scheda completa:
Link al Full Text:
Pubblicato in: