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
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期刊论文
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发表日期:
2024年1月18日
- 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
摘要
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.