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

Link

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

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