| Title: |
X-chromosome and kidney function : evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements |
| Authors: |
Scholz, Markus; Horn, Katrin; Pott, Janne; Wuttke, Matthias; Kühnapfel, Andreas; Nasr, M. Kamal; Kirsten, Holger; Li, Yong; Hoppmann, Anselm; Gorski, Mathias; Ghasemi, Sahar; Li, Man; Tin, Adrienne; Chai, Jin Fang; Cocca, Massimiliano; Wang, Judy; Nutile, Teresa; Akiyama, Masato; Åsvold, Bjørn Olav; Bansal, Nisha; Biggs, Mary L.; Boutin, Thibaud; Brenner, Hermann; Brumpton, Ben; Burkhardt, Ralph; Cai, Jianwen; Campbell, Archie; Campbell, Harry; Chalmers, John; Chasman, Daniel I.; Chee, Miao Ling; Chee, Miao Li; Chen, Xu; Cheng, Ching Yu; Cifkova, Renata; Daviglus, Martha; Delgado, Graciela; Dittrich, Katalin; Edwards, Todd L.; Endlich, Karlhans; Michael Gaziano, J.; Giri, Ayush; Giulianini, Franco; Gordon, Scott D.; Gudbjartsson, Daniel F.; Hallan, Stein; Hamet, Pavel; Hartman, Catharina A.; Hayward, Caroline; Heid, Iris M.; Hellwege, Jacklyn N.; Holleczek, Bernd; Holm, Hilma; Hutri-Kähönen, Nina; Hveem, Kristian; Isermann, Berend; Jonas, Jost B.; Joshi, Peter K.; Kamatani, Yoichiro; Kanai, Masahiro; Kastarinen, Mika; Khor, Chiea Chuen; Kiess, Wieland; Kleber, Marcus E.; Körner, Antje; Kovacs, Peter; Krajcoviechova, Alena; Kramer, Holly; Krämer, Bernhard K.; Kuokkanen, Mikko; Kähönen, Mika; Lange, Leslie A.; Lash, James P.; Lehtimäki, Terho; Li, Hengtong; Lin, Bridget M.; Liu, Jianjun; Loeffler, Markus; Lyytikäinen, Leo Pekka; Magnusson, Patrik K.E.; Martin, Nicholas G.; Matsuda, Koichi; Milaneschi, Yuri; Mishra, Pashupati P.; Mononen, Nina; Montgomery, Grant W.; Mook-Kanamori, Dennis O.; Mychaleckyj, Josyf C.; März, Winfried; Nauck, Matthias; Nikus, Kjell; Nolte, Ilja M.; Noordam, Raymond; Okada, Yukinori; Olafsson, Isleifur; Oldehinkel, Albertine J.; Penninx, Brenda W.J.H.; Perola, Markus; Pirastu, Nicola; Polasek, Ozren; Porteous, David J.; Poulain, Tanja; Psaty, Bruce M.; Rabelink, Ton J.; Raffield, Laura M.; Raitakari, Olli T.; Rasheed, Humaira; Reilly, Dermot F.; Rice, Kenneth M.; Richmond, Anne; Ridker, Paul M.; Rotter, Jerome I.; Rudan, Igor; Sabanayagam, Charumathi; Salomaa, Veikko; Schneiderman, Neil; Schöttker, Ben; Sims, Mario; Snieder, Harold; Stark, Klaus J.; Stefansson, Kari; Stocker, Hannah; Stumvoll, Michael; Sulem, Patrick; Sveinbjornsson, Gardar; Svensson, Per O.; Tai, E. Shyong; Taylor, Kent D.; Tayo, Bamidele O.; Teren, Andrej; Tham, Yih Chung; Thiery, Joachim; Thio, Chris H.L.; Thomas, Laurent F.; Tremblay, Johanne; Tönjes, Anke; van der Most, Peter J.; Vitart, Veronique; Völker, Uwe; Wang, Ya Xing; Wang, Chaolong; Wei, Wen Bin; Whitfield, John B.; Wild, Sarah H.; Wilson, James F.; Winkler, Thomas W.; Wong, Tien Yin; Woodward, Mark; Sim, Xueling; Chu, Audrey Y.; Feitosa, Mary F.; Thorsteinsdottir, Unnur; Hung, Adriana M.; Teumer, Alexander; Franceschini, Nora; Parsa, Afshin; Köttgen, Anna; Schlosser, Pascal; Pattaro, Cristian |
| Contributors: |
Research Programs Unit; CAMM - Research Program for Clinical and Molecular Metabolism |
| Publisher Information: |
Nature Publishing Group |
| Publication Year: |
2024 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Biomedicine |
| Description: |
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
This project was supported by the German Research Foundation (DFG) Project-ID 431984000 (SFB 1453 A.Köt., P.S.), 523737608 (P.S.), and 209933838 (SFB1052 M.S.) and the German Federal Ministry of Education and Research (BMBF, #01ZX1906B, project “SYMPATH”, K.H.). D.F.G., H.H., I.O., K.S., P.Su., G.S., and U.T. are employees of deCODE/Amgen Inc. M.E.K. is employed with Synlab Holding Deutschland GmbH. W.M. is employed with Synlab Services GmbH and holds shares of Synlab Holding Deutschland GmbH. B.M.P. serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. D.R. is currently an employee of Janssen Pharmaceuticals Inc. M.S. received funding from Pfizer Inc. for a project not related to this research. The remaining authors declare no competing interests.; https://hdl.handle.net/10138/571181; 85182684565; 001187887400001 |
| Availability: |
https://hdl.handle.net/10138/571181 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.8EA557C2 |
| Database: |
BASE |