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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;
- 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;
- Bansal, Nisha;
- Biggs, Mary;
- Boutin, Thibaud;
- Brenner, Hermann;
- Brumpton, Ben;
- Burkhardt, Ralph;
- Cai, Jianwen;
- Campbell, Archie;
- Campbell, Harry;
- Chalmers, John;
- Chasman, Daniel;
- Chee, Miao;
- Chee, Miao;
- Chen, Xu;
- Cheng, Ching-Yu;
- Cifkova, Renata;
- Daviglus, Martha;
- Delgado, Graciela;
- Dittrich, Katalin;
- Edwards, Todd;
- Endlich, Karlhans;
- Michael Gaziano, J;
- Giri, Ayush;
- Giulianini, Franco;
- Gordon, Scott;
- Gudbjartsson, Daniel;
- Hallan, Stein;
- Hamet, Pavel;
- Hartman, Catharina;
- Hayward, Caroline;
- Heid, Iris;
- Hellwege, Jacklyn;
- Holleczek, Bernd;
- Holm, Hilma;
- Hutri-Kähönen, Nina;
- Hveem, Kristian;
- Isermann, Berend;
- Jonas, Jost;
- Joshi, Peter;
- Kamatani, Yoichiro;
- Kanai, Masahiro;
- Kastarinen, Mika;
- Khor, Chiea;
- Kiess, Wieland;
- Kleber, Marcus;
- Körner, Antje;
- Kovacs, Peter;
- Krajcoviechova, Alena;
- Kramer, Holly;
- Krämer, Bernhard;
- Kuokkanen, Mikko;
- Kähönen, Mika;
- Lange, Leslie;
- Lash, James;
- Lehtimäki, Terho;
- Li, Hengtong;
- Lin, Bridget;
- Liu, Jianjun;
- Loeffler, Markus;
- Lyytikäinen, Leo-Pekka;
- Magnusson, Patrik;
- Martin, Nicholas;
- Matsuda, Koichi;
- Milaneschi, Yuri;
- Mishra, Pashupati;
- Mononen, Nina;
- Montgomery, Grant;
- Mook-Kanamori, Dennis;
- Mychaleckyj, Josyf;
- März, Winfried;
- Nauck, Matthias;
- Nikus, Kjell;
- Nolte, Ilja;
- Noordam, Raymond;
- Okada, Yukinori;
- Olafsson, Isleifur;
- Oldehinkel, Albertine;
- Penninx, Brenda;
- Perola, Markus;
- Pirastu, Nicola;
- Polasek, Ozren;
- Porteous, David;
- Poulain, Tanja;
- Psaty, Bruce;
- Rabelink, Ton;
- Raffield, Laura;
- Raitakari, Olli;
- Rasheed, Humaira;
- Reilly, Dermot;
- Rice, Kenneth;
- Richmond, Anne;
- Ridker, Paul;
- Rudan, Igor;
- Sabanayagam, Charumathi;
- Salomaa, Veikko;
- Schneiderman, Neil;
- Schöttker, Ben;
- Sims, Mario;
- Snieder, Harold;
- Stark, Klaus;
- Stefansson, Kari;
- Stocker, Hannah;
- Stumvoll, Michael;
- Sulem, Patrick;
- Sveinbjornsson, Gardar;
- Svensson, Per;
- Tai, E-Shyong;
- Taylor, Kent;
- Tayo, Bamidele;
- Teren, Andrej;
- Tham, Yih-Chung;
- Thiery, Joachim;
- Thio, Chris;
- Thomas, Laurent;
- Tremblay, Johanne;
- Tönjes, Anke;
- van der Most, Peter;
- Vitart, Veronique;
- Völker, Uwe;
- Wang, Ya;
- Wang, Chaolong;
- Wei, Wen;
- Whitfield, John;
- Wild, Sarah;
- Wilson, James;
- Winkler, Thomas;
- Wong, Tien-Yin;
- Woodward, Mark;
- Sim, Xueling;
- Chu, Audrey;
- Feitosa, Mary;
- Thorsteinsdottir, Unnur;
- Hung, Adriana;
- Teumer, Alexander;
- Franceschini, Nora;
- Parsa, Afshin;
- Köttgen, Anna;
- Schlosser, Pascal;
- Pattaro, Cristian;
- Rotter, Jerome
- et al.
Published Web Location
https://doi.org/10.1038/s41467-024-44709-1Abstract
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.
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