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
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 (2024-01-18)
18.01.2024
Nature Communications
586
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202405306483
https://urn.fi/URN:NBN:fi:tuni-202405306483
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [24232]