학술논문
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.
Document Type
article
Author
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; 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
Source
Nature Communications. 15(1)
Subject
Language
Abstract
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.