Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure
Academic Article
Publication Date:
2024
Short description:
Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure / Ganji-Arjenaki, M., Kamali, Z., Evangelou, E., Warren, H.R., Gao, H., Ntritsos, G., Dimou, N., Esko, T., Magi, R., Milani, L., Almgren, P., Boutin, T., Debette, S., Ding, J., Giulianini, F., Holliday, E.G., Jackson, A.U., Li -Gao, R., Lin, W.-Y., Luan, J., et al.. - In: KIDNEY INTERNATIONAL REPORTS. - ISSN 2468-0249. - 9:6(2024), pp. 1849-1859. [10.1016/j.ekir.2024.03.001]
abstract:
Introduction: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP. Methods: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years. Results: Our analyses prioritized myofibroblasts and endothelial cells, among the total of 33 annotated cell type, as specifically involved in BP regulation (P < 0.05/33, i.e., 0.001515). Enrichment of heritability for systolic BP (SBP) was observed in myofibroblast cells in mature human kidney cortex, and enrichment of heritability for diastolic BP (DBP) was observed in descending vasa recta and peritubular capillary endothelial cells as well as stromal myofibroblast cells. The new finding of myofibroblast, the significant cell type for both BP traits, was consistent in 8 replication efforts using 7 sets of independent data, including in human fetal kidney, in East-Asian (EAS) ancestry, using mouse single-cell RNA sequencing (scRNA-seq) data, and when using another prioritization method. Conclusion: Our findings provide a solid basis for follow-up studies to further identify genes and mechanisms in myofibroblast cells that underlie the regulation of BP.
Iris type:
1.1 Articolo in rivista
Keywords:
blood pressure; cell-type; genome; kidney myofibroblast; scRNA-seq
List of contributors:
Ganji-Arjenaki, M.; Kamali, Z.; Evangelou, E.; Warren, H. R.; Gao, H.; Ntritsos, G.; Dimou, N.; Esko, T.; Magi, R.; Milani, L.; Almgren, P.; Boutin, T.; Debette, S.; Ding, J.; Giulianini, F.; Holliday, E. G.; Jackson, A. U.; Li -Gao, R.; Lin, W. -Y.; Luan, J.; Mangino, M.; Oldmeadow, C.; Prins, B. P.; Qian, Y.; Sargurupremraj, M.; Shah, N.; Surendran, P.; Theriault, S.; Verweij, N.; Willems, S. M.; Zhao, J. -H.; Amouyel, P.; Connell, J.; de Mutsert, R.; Doney, A. S. F.; Farrall, M.; Menni, C.; Morris, A. D.; Noordam, R.; Pare, G.; Poulter, N. R.; Shields, D. C.; Stanton, A.; Thom, S.; Abecasis, G.; Amin, N.; Arking, D. E.; Ayers, K. L.; Barbieri, C. M.; Batini, C.; Bis, J. C.; Blake, T.; Bochud, M.; Boehnke, M.; Boerwinkle, E.; Boomsma, D. I.; Bottinger, E. P.; Braund, P. S.; Brumat, M.; Campbell, A.; Campbell, H.; Chakravarti, A.; Chambers, J. C.; Chauhan, G.; Ciullo, M.; Cocca, M.; Collins, F.; Cordell, H. J.; Davies, G.; de Borst, M. H.; de Geus, E. J.; Deary, I. J.; Deelen, J.; Del Greco M, F.; Demirkale, C. Y.; Dorr, M.; Ehret, G. B.; Elosua, R.; Enroth, S.; Erzurumluoglu, A. M.; Ferreira, T.; Franberg, M.; Franco, O. H.; Gandin, I.; Gasparini, P.; Giedraitis, V.; Gieger, C.; Girotto, G.; Goel, A.; Gow, A. J.; Gudnason, V.; Guo, X.; Gyllensten, U.; Hamsten, A.; Harris, T. B.; Harris, S. E.; Hartman, C. A.; Havulinna, A. S.; Hicks, A. A.; Hofer, E.; Hofman, A.; Hottenga, J. -J.; Huffman, J. E.; Hwang, S. -J.; Ingelsson, E.; James, A.; Jansen, R.; Jarvelin, M. -R.; Joehanes, R.; Johansson, A.; Johnson, A. D.; Joshi, P. K.; Jousilahti, P.; Jukema, J. W.; Jula, A.; Kahonen, M.; Kathiresan, S.; Keavney, B. D.; Khaw, K. -T.; Knekt, P.; Knight, J.; Kolcic, I.; Kooner, J. S.; Koskinen, S.; Kristiansson, K.; Kutalik, Z.; Laan, M.; Larson, M.; Launer, L. J.; Lehne, B.; Lehtimaki, T.; Liewald, D. C. M.; Lin, L.; Lind, L.; Lindgren, C. M.; Liu, Y.; Loos, R. J. F.; Lopez, L. M.; Lu, Y.; Lyytikainen, L. -P.; Mahajan, A.; Mamasoula, C.; Marrugat, J.; Marten, J.; Milaneschi, Y.; Morgan, A.; Morris, A. P.; Morrison, A. C.; Munson, P. J.; Nalls, M. A.; Nandakumar, P.; Nelson, C. P.; Niiranen, T.; Nolte, I. M.; Nutile, T.; Oldehinkel, A. J.; Oostra, B. A.; O'Reilly, P. F.; Org, E.; Padmanabhan, S.; Palmas, W.; Palotie, A.; Pattie, A.; Penninx, B. W. J. H.; Perola, M.; Peters, A.; Polasek, O.; Pramstaller, P. P.; Nguyen, Q. T.; Raitakari, O. T.; Rettig, R.; Rice, K.; Ridker, P. M.; Ried, J. S.; Riese, H.; Ripatti, S.; Robino, A.; Rose, L. M.; Rotter, J. I.; Rudan, I.; Ruggiero, D.; Saba, Y.; Sala, C. F.; Salomaa, V.; Samani, N. J.; Sarin, A. -P.; Schmidt, R.; Schmidt, H.; Shrine, N.; Siscovick, D.; Smith, A. V.; Snieder, H.; Sober, S.; Sorice, R.; Starr, J. M.; Stott, D. J.; Strachan, D. P.; Strawbridge, R. J.; Sundstrom, J.; Swertz, M. A.; Taylor, K. D.; Teumer, A.; Tobin, M. D.; Tomaszewski, M.; Toniolo, D.; Traglia, M.; Trompet, S.; Tuomilehto, J.; Tzourio, C.; Uitterlinden, A. G.; Vaez, A.; van der Most, P. J.; van Duijn, C. M.; Verwoert, G. C.; Vitart, V.; Volker, U.; Vollenweider, P.; Vuckovic, D.; Watkins, H.; Wild, S. H.; Willemsen, G.; Wilson, J. F.; Wright, A. F.; Yao, J.; Zemunik, T.; Zhang, W.; Attia, J. R.; Butterworth, A. S.; Chasman, D. I.; Conen, D.; Cucca, F.; Danesh, J.; Hayward, C.; Howson, J. M. M.; Laakso, M.; Lakatta, E. G.; Langenberg, C.; Melander, O.; Mook-Kanamori, D. O.; Palmer, C. N. A.; Risch, L.; Scott, R. A.; Scott, R. J.; Sever, P.; Spector, T. D.; van der Harst, P.; Wareham, N. J.; Zeggini, E.; Levy, D.; Munroe, P. B.; Newton-Cheh, C.; Brown, M. J.; Metspalu, A.; Psaty, B. M.; Wain, L. V.; Elliott, P.; Caulfield, M. J.; Sardari, S.; de Borst, M.
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