Yask Gupta, David J Friedman, Michelle T McNulty, Atlas Khan, Brandon Lane, Chen Wang, Juntao Ke, Gina Jin, Benjamin Wooden, Andrea L Knob, Tze Y Lim, Gerald B Appel, Kinsie Huggins, Lili Liu, Adele Mitrotti, Megan C Stangl, Andrew Bomback, Rik Westland, Monica Bodria, Maddalena Marasa, Ning Shang, David J Cohen, Russell J Crew, William Morello, Pietro Canetta, Jai Radhakrishnan, Jeremiah Martino, Qingxue Liu, Wendy K Chung, Angelica Espinoza, Yuan Luo, Wei-Qi Wei, Qiping Feng, Chunhua Weng, Yilu Fang, Iftikhar J Kullo, Mohammadreza Naderian, Nita Limdi, Marguerite R Irvin, Hemant Tiwari, Sumit Mohan, Maya Rao, Geoffrey K Dube, Ninad S Chaudhary, Orlando M Gutiérrez, Suzanne E Judd, Mary Cushman, Leslie A Lange, Ethan M Lange, Daniel L Bivona, Miguel Verbitsky, Cheryl A Winkler, Jeffrey B Kopp, Dominick Santoriello, Ibrahim Batal, Sérgio Veloso Brant Pinheiro, Eduardo Araújo Oliveira, Ana Cristina Simoes E Silva, Isabella Pisani, Enrico Fiaccadori, Fangming Lin, Loreto Gesualdo, Antonio Amoroso, Gian Marco Ghiggeri, Vivette D D'Agati, Riccardo Magistroni, Eimear E Kenny, Ruth J F Loos, Giovanni Montini, Friedhelm Hildebrandt, Dirk S Paul, Slavé Petrovski, David B Goldstein, Matthias Kretzler, Rasheed Gbadegesin, Ali G Gharavi, Krzysztof Kiryluk, Matthew G Sampson, Martin R Pollak, Simone Sanna-Cherchi
African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk...
November 30, 2023: Nature Communications