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
Creators: name: Isermann, Berend
name: Köttgen, Anna
name: Nutile, Teresa
name: Cifkova, Renata
name: Raitakari, Olli T.
name: Giulianini, Franco
name: Winkler, Thomas W.
name: Scholz, Markus
name: Stocker, Hannah
name: Chu, Audrey Y.
name: Noordam, Raymond
name: Sabanayagam, Charumathi
name: Pott, Janne
name: Burkhardt, Ralph
name: Tremblay, Johanne
name: Brumpton, Ben
name: Kähönen, Mika
name: Wei, Wen Bin
name: Wuttke, Matthias
name: Holleczek, Bernd
name: Tham, Yih-Chung
name: Cheng, Ching-Yu
name: Teumer, Alexander
name: Michael Gaziano, J.
name: Hoppmann, Anselm
name: Tin, Adrienne
name: Sulem, Patrick
name: Kirsten, Holger
name: Stark, Klaus J.
name: Rudan, Igor
name: Magnusson, Patrik K. E.
name: Khor, Chiea Chuen
name: Perola, Markus
name: Tönjes, Anke
name: Liu, Jianjun
name: Hayward, Caroline
name: Li, Man
name: Wang, Judy
name: Chee, Miao Li
name: Dittrich, Katalin
name: Lyytikäinen, Leo-Pekka
name: Schlosser, Pascal
name: Åsvold, Bjørn Olav
name: Woodward, Mark
name: Biggs, Mary L.
name: Penninx, Brenda W. J. H.
name: Svensson, Per O.
name: Krämer, Bernhard K.
name: Campbell, Archie
name: Montgomery, Grant W.
name: Kanai, Masahiro
name: Thomas, Laurent F.
name: Delgado, Graciela
name: Matsuda, Koichi
name: Mishra, Pashupati P.
name: Joshi, Peter K.
name: Hamet, Pavel
name: Lash, James P.
name: Li, Hengtong
name: Li, Yong
name: Chalmers, John
name: Bansal, Nisha
name: Rasheed, Humaira
name: Gordon, Scott D.
name: Chasman, Daniel I.
name: Wild, Sarah H.
name: Hutri-Kähönen, Nina
name: Nikus, Kjell
name: Porteous, David J.
name: Tai, E-Shyong
name: Stumvoll, Michael
name: Milaneschi, Yuri
name: Schneiderman, Neil
name: Kleber, Marcus E.
name: Kovacs, Peter
name: Rotter, Jerome I.
name: Tayo, Bamidele O.
name: Gudbjartsson, Daniel F.
name: Psaty, Bruce M.
name: Holm, Hilma
name: Hveem, Kristian
name: Parsa, Afshin
name: Ghasemi, Sahar
name: Whitfield, John B.
name: Raffield, Laura M.
name: Wang, Chaolong
name: März, Winfried
name: van der Most, Peter J.
name: Brenner, Hermann
name: Kramer, Holly
name: Kuokkanen, Mikko
name: Hellwege, Jacklyn N.
name: Rice, Kenneth M.
name: Chen, Xu
name: Jonas, Jost B.
name: Hung, Adriana M.
name: Endlich, Karlhans
name: Okada, Yukinori
name: Kühnapfel, Andreas
name: Wang, Ya Xing
name: Lange, Leslie A.
name: Nasr, M. Kamal
name: Snieder, Harold
name: Heid, Iris M.
name: Reilly, Dermot F.
name: Lehtimäki, Terho
name: Thiery, Joachim
name: Hartman, Catharina A.
name: Gorski, Mathias
name: Körner, Antje
name: Giri, Ayush
name: Cocca, Massimiliano
name: Wilson, James F.
name: Thorsteinsdottir, Unnur
name: Franceschini, Nora
name: Nolte, Ilja M.
name: Akiyama, Masato
name: Oldehinkel, Albertine J.
name: Salomaa, Veikko
name: Sveinbjornsson, Gardar
name: Cai, Jianwen
name: Mononen, Nina
name: Daviglus, Martha
name: Martin, Nicholas G.
name: Rabelink, Ton J.
name: Teren, Andrej
name: Campbell, Harry
name: Pattaro, Cristian
name: Boutin, Thibaud
name: Feitosa, Mary F.
name: Nauck, Matthias
name: Ridker, Paul M.
name: Horn, Katrin
name: Polasek, Ozren
name: Kastarinen, Mika
name: Kamatani, Yoichiro
name: Völker, Uwe
name: Lin, Bridget M.
name: Kiess, Wieland
name: Chai, Jin-Fang
name: Mook-Kanamori, Dennis O.
name: Taylor, Kent D.
name: Chee, Miao Ling
name: Loeffler, Markus
name: Wong, Tien-Yin
name: Stefansson, Kari
name: Poulain, Tanja
name: Sim, Xueling
name: Pirastu, Nicola
name: Richmond, Anne
name: Vitart, Veronique
name: Sims, Mario
name: Schöttker, Ben
name: Krajcoviechova, Alena
name: Olafsson, Isleifur
name: Mychaleckyj, Josyf C.
name: Thio, Chris H. L.
name: Hallan, Stein
name: Edwards, Todd L.
Publisher: name: Springer Nature
Year: 2024

description: <p>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&thinsp;=&thinsp;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.</p>