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-Reference-Cited by-同舟云学术

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

Published:2024-01-18 Issue:1 Volume:15 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

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

Abstract

AbstractX-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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Link

https://www.nature.com/articles/s41467-024-44709-1.pdf

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