Portal de Periódicos da CAPES

An eQTL Landscape of Kidney Tissue in Human Nephrotic Syndrome

2018; Elsevier BV; Volume: 103; Issue: 2 Linguagem: Inglês

10.1016/j.ajhg.2018.07.004

1537-6605

Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar A. Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle Mcnulty, Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, John R. Sedor, Katherine M. Dell, M. Schachere, Kevin V. Lemley, L Whitted, Tarak Srivastava, Connie J Haney, Christine B. Sethna, Kalliopi Grammatikopoulos, Gerald B. Appel, Michael Toledo, Laurence Greenbaum, Chia-shi Wang, Brian Lee, Sharon G. Adler, Cynthia C. Nast, Janine LaPage, Ambarish M. Athavale, Alicia M. Neu, Sara A. Boynton, Fernando C. Fervenza, Marie C. Hogan, John C. Lieske, Vladimir Chernitskiy, Frederick J. Kaskel, Neelja Kumar, P. Flynn, Jeffrey B. Kopp, E Castro-Rubio, J. Thomas Blake, Howard Trachtman, Olga Zhdanova, Frank Modersitzki, Suzanne Vento, Richard A. Lafayette, Kshama Mehta, Crystal A. Gadegbeku, Duncan B. Johnstone, Daniel C. Cattran, Michelle Hladunewich, Heather N. Reich, Paul Ling, Martin Romano, Alessia Fornoni, Laura Barisoni, Carlos Bidot, Matthias Kretzler, Debbie S. Gipson, Amanda Williams, Renée Pitter, Patrick H. Nachman, Keisha Gibson, S Grubbs, Anne Froment, Lawrence B. Holzman, Kevin Meyers, K. Kallem, Fumei Cerecino, Kamal Sambandam, Elizabeth Brown, Natalie Johnson, A. Jefferson, Sangeeta Hingorani, Katherine R. Tuttle, Laura Curtin, S. Dismuke, Ann Cooper, Barry I. Freedman, Jen Jar Lin, S Gray, Matthias Kretzler, L. Barisoni, Crystal A. Gadegbeku, Brenda W. Gillespie, Debbie S. Gipson, Lawrence B. Holzman, Laura Mariani, Matthew G. Sampson, Peter X.‐K. Song, Johnathan Troost, Jarcy Zee, Emily Herreshoff, Colleen Kincaid, Chrysta Lienczewski, T. Mainieri, Amanda Williams, Kevin C. Abbott, Cindy N. Roy, Tiina K. Urv, John S. Brooks,

Amyloidosis: Diagnosis, Treatment, Outcomes

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis -eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian "Deterministic Approximation of Posteriors" (DAP) to fine-map these signals, eQTLBMA to discover GLOM- or TI-specific eQTLs, and single-cell RNA-seq data of control kidney tissue to identify the cell type specificity of significant eQTLs. We integrated eQTL data with an IgA Nephropathy (IgAN) GWAS to perform a transcriptome-wide association study (TWAS). We discovered 894 GLOM eQTLs and 1,767 TI eQTLs at FDR < 0.05. 14% and 19% of GLOM and TI eQTLs, respectively, had >1 independent signal associated with its expression. 12% and 26% of eQTLs were GLOM specific and TI specific, respectively. GLOM eQTLs were most significantly enriched in podocyte transcripts and TI eQTLs in proximal tubules. The IgAN TWAS identified significant GLOM and TI genes, primarily at the HLA region. In this study, we discovered GLOM and TI eQTLs, identified those that were tissue specific, deconvoluted them into cell-specific signals, and used them to characterize known GWAS alleles. These data are available for browsing and download via our eQTL browser, "nephQTL."