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
Markus Scholz; Katrin Horn; Janne Pott; Matthias Wuttke; Andreas Kühnapfel; M. Kamal Nasr; Holger Kirsten; Yong Li; Anselm Hoppmann; Mathias Gorski; Sahar Ghasemi; Man Li; Adrienne Tin; Jin-Fang Chai; Massimiliano Cocca; Judy Wang; Teresa Nutile; Masato Akiyama; Bjørn Olav Åsvold; Nisha Bansal; Mary L. Biggs; Thibaud Boutin; Hermann Brenner; Ben Brumpton; Ralph Burkhardt; Jianwen Cai; Archie Campbell; Harry Campbell; John Chalmers; Daniel I. Chasman; Miao Ling Chee; Miao Li Chee; Xu Chen; Ching-Yu Cheng; Renata Cifkova; Martha Daviglus; Graciela Delgado; Katalin Dittrich; Todd L. Edwards; Karlhans Endlich; J. Michael Gaziano; Ayush Giri; Franco Giulianini; Scott D. Gordon; Daniel F. Gudbjartsson; Stein Hallan; Pavel Hamet; Catharina A. Hartman; Caroline Hayward; Iris M. Heid; Jacklyn N. Hellwege; Bernd Holleczek; Hilma Holm; Nina Hutri-Kähönen; Kristian Hveem; Berend Isermann; Jost B. Jonas; Peter K. Joshi; Yoichiro Kamatani; Masahiro Kanai; Mika Kastarinen; Chiea Chuen Khor; Wieland Kiess; Marcus E. Kleber; Antje Körner; Peter Kovacs; Alena Krajcoviechova; Holly Kramer; Bernhard K. Krämer; Mikko Kuokkanen; Mika Kähönen; Leslie A. Lange; James P. Lash; Terho Lehtimäki; Hengtong Li; Bridget M. Lin; Jianjun Liu; Markus Loeffler; Leo-Pekka Lyytikäinen; Patrik K. E. Magnusson; Nicholas G. Martin; Koichi Matsuda; Yuri Milaneschi; Pashupati P. Mishra; Nina Mononen; Grant W. Montgomery; Dennis O. Mook-Kanamori; Josyf C. Mychaleckyj; Winfried März; Matthias Nauck; Kjell Nikus; Ilja M. Nolte; Raymond Noordam; Yukinori Okada; Isleifur Olafsson; Albertine J. Oldehinkel; Brenda W. J. H. Penninx; Markus Perola; Nicola Pirastu; Ozren Polasek; David J. Porteous; Tanja Poulain; Bruce M. Psaty; Ton J. Rabelink; Laura M. Raffield; Olli T. Raitakari; Humaira Rasheed; Dermot F. Reilly; Kenneth M. Rice; Anne Richmond; Paul M. Ridker; Jerome I. Rotter; Igor Rudan; Charumathi Sabanayagam; Veikko Salomaa; Neil Schneiderman; Ben Schöttker; Mario Sims; Harold Snieder; Klaus J. Stark; Kari Stefansson; Hannah Stocker; Michael Stumvoll; Patrick Sulem; Gardar Sveinbjornsson; Per O. Svensson; E-Shyong Tai; Kent D. Taylor; Bamidele O. Tayo; Andrej Teren; Yih-Chung Tham; Joachim Thiery; Chris H. L. Thio; Laurent F. Thomas; Johanne Tremblay; Anke Tönjes; Peter J. van der Most; Veronique Vitart; Uwe Völker; Ya Xing Wang; Chaolong Wang; Wen Bin Wei; John B. Whitfield; Sarah H. Wild; James F. Wilson; Thomas W. Winkler; Tien-Yin Wong; Mark Woodward; Xueling Sim; Audrey Y. Chu; Mary F. Feitosa; Unnur Thorsteinsdottir; Adriana M. Hung; Alexander Teumer; Nora Franceschini; Afshin Parsa; Anna Köttgen; Pascal Schlosser; Cristian Pattaro
Source
Nature Communications, Vol 15, Iss 1, Pp 1-17 (2024)
Subject
Language
English
ISSN
2041-1723
Abstract
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.