Genetic Susceptibility to IgA Nephropathy (Version 1.0)

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Krzysztof Kiryluk, MD, MS and David A. Fasel

Use this calculator to determine an individual's risk of developing IgA nephropathy based on specific genetic markers. The risk score equation is based on the 7 SNPs associated with IgA nephropathy in the analysis of 10,755 individuals from 12 international case-control cohorts. These cohorts include individuals of European, Asian, and African ancestry. The risk score is standardized using genotypes of 1,050 individuals from 52 worldwide populations included in the Human Genome Diversity Project (HGDP). You may also use the newer 15 SNP calculator (version 2.0).

To calculate the disease risk, select the genotypes from the drop-down menus:

SNP [Risk Allele]	Genotype
rs6677604 [G]
rs9275224 [G]
rs2856717 [T]
rs9275596 [T]
rs9357155 [G]
rs1883414 [C]
rs2412971 [G]

Please enter a value for all 7 SNPs listed above.

Standardized
IgA Nephropathy Risk:

Select SNP genotypes to calculate risk.

Interpretation:

Standardized risk score represents the number of standard deviations away from the worldwide mean. For each unit of standardized risk score, the risk of IgA nephropathy changes by 47.4%. Population average is based on the average risk score across 52 worldwide populations represented in the HGDP panel. Average risk is defined as less than one standard deviation from the worldwide mean.

Risk Score Equation:

Standardized Genetic Risk =
[-0.46 × N(rs6677604:A) - 0.31 × N(rs9275224:A) + 0.42 × N(rs2856717:T) - 0.47 × N(rs9275596:C) - 0.23 × N(rs9357155:A) - 0.16 × N(rs1883414:T) - 0.27 × N(rs2412971:A) + 0.18 × N(rs6677604:A) × N(rs2412971:A) – Worldwide Mean] / (Worldwide SD)

N = number of reference alleles for each SNP (0, 1, or 2 per individual genotype).
Worldwide Mean = -0.8360883 = mean risk score based on the HGDP data.
Worldwide SD = 0.4146805 = risk score standard deviation based on the HGDP data.

References:

Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M, Suzuki H, Eitner F, Snyder HJ, Choi M, Hou P, Scolari F, Izzi C, Gigante M, Gesualdo L, Savoldi S, Amoroso A, Cusi D, Zamboli P, Julian BA, Novak J, Wyatt RJ, Mucha K, Perola M, Kristiansson K, Viktorin A, Magnusson PK, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Boland A, Metzger M, Thibaudin L, Wanner C, Jager KJ, Goto S, Maixnerova D, Karnib HH, Nagy J, Panzer U, Xie J, Chen N, Tesar V, Narita I, Berthoux F, Floege J, Stengel B, Zhang H, Lifton RP, and Gharavi AG: Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis. PLoS Genetics 2012; 8(6):e1002765.

Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola F, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano SP, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP: Genome-wide Association Study Identifies Susceptibility Loci for IgA Nephropathy. Nat Genet. 2011; 43(4):321-7.

Disclaimer:

This tool is designed for individual risk prediction, however, it does not imply medical advice and it should not be used to guide clinical management until additional studies confirm its clinical utility. This risk assessment may not be applicable to all populations. Please refer to the original publication for detailed characteristics of the populations used for risk score discovery.

Last updated 8/2012