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Nature communications, 2020.11(1), 1600-0, DOI: https://doi.org/10.1038/s41467-020-15383-w
The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis
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 X S;Sampson MG;Mariani LH;Perkowska-Ptasinska A;Durlik M;Mucha K;Moszczuk B;Foroncewicz B;P?czek L;Habura I;Ars E;Ballarin J;Mani LY;Vogt B;Ozturk S;Yildiz A;Seyahi N;Arikan H;Koc M;Sever M;Basturk T;Karahan G;Akgul S;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 Y;Kim D;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;Kottgen 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 L;Lee H;Hoxha E;Stahl RAK;Brenchley P;Scolari F;Zhao MH;Ali G Gharavi AG;Kleta R;Chen N;Kiryluk K
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), finemap 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.
- DOI: https://doi.org/10.1038/s41467-020-15383-w
- ISBN or ISSN: 2041-1723
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.