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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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| Titill: | 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 |
| Höfundur: |
... 149 fleiri höfundar Sýna alla höfunda |
| Útgáfa: | 2024-01-18 |
| Tungumál: | Enska |
| Umfang: | 4409238 |
| Svið: | Health Sciences |
| Deild: | Other departments Faculty of Medicine |
| Birtist í: | Nature Communications; 15(1) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-024-44709-1 |
| Efnisorð: | Lífefna- og sameindalíffræði; Humans; Male; Female; Androgens/genetics; Genome-Wide Association Study; Kidney; Chromosomes, Human, X/genetics; Response Elements; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Tetraspanins/genetics; General Chemistry; General Biochemistry,Genetics and Molecular Biology; General Physics and Astronomy |
| URI: | https://hdl.handle.net/20.500.11815/4705 |
Tilvitnun:Scholz , M , Horn , K , Pott , J , Wuttke , M , Kühnapfel , A , Nasr , M K , Kirsten , H , Li , Y , Hoppmann , A , Gorski , M , Ghasemi , S , Li , M , Tin , A , Chai , J F , Cocca , M , Wang , J , Nutile , T , Akiyama , M , Åsvold , B O , Bansal , N , Biggs , M L , Boutin , T , Brenner , H , Brumpton , B , Burkhardt , R , Cai , J , Campbell , A , Campbell , H , Chalmers , J , Chasman , D I , Chee , M L , Chee , M L , Chen , X , Cheng , C Y , Cifkova , R , Daviglus , M , Delgado , G , Dittrich , K , Edwards , T L , Endlich , K , Michael Gaziano , J , Giri , A , Giulianini , F , Gordon , S D , Gudbjartsson , D F , Hallan , S , Hamet , P , Hartman , C A , Hayward , C , Heid , I M , Hellwege , J N , Holleczek , B , Holm , H , Hutri-Kähönen , N , Hveem , K , Isermann , B , Jonas , J B , Joshi , P K , Kamatani , Y , Kanai , M , Kastarinen , M , Khor , C C , Kiess , W , Kleber , M E , Körner , A , Kovacs , P , Krajcoviechova , A , Kramer , H , Krämer , B K , Kuokkanen , M , Kähönen , M , Lange , L A , Lash , J P , Lehtimäki , T , Li , H , Lin , B M , Liu , J , Loeffler , M , Lyytikäinen , L P , Magnusson , P K E , Martin , N G , Matsuda , K , Milaneschi , Y , Mishra , P P , Mononen , N , Montgomery , G W , Mook-Kanamori , D O , Mychaleckyj , J C , März , W , Nauck , M , Nikus , K , Nolte , I M , Noordam , R , Okada , Y , Ólafsson , Í , Oldehinkel , A J , Penninx , B W J H , Perola , M , Pirastu , N , Polasek , O , Porteous , D J , Poulain , T , Psaty , B M , Rabelink , T J , Raffield , L M , Raitakari , O T , Rasheed , H , Reilly , D F , Rice , K M , Richmond , A , Ridker , P M , Rotter , J I , Rudan , I , Sabanayagam , C , Salomaa , V , Schneiderman , N , Schöttker , B , Sims , M , Snieder , H , Stark , K J , Stefánsson , K , Stocker , H , Stumvoll , M , Sulem , P , Sveinbjornsson , G , Svensson , P O , Tai , E S , Taylor , K D , Tayo , B O , Teren , A , Tham , Y C , Thiery , J , Thio , C H L , Thomas , L F , Tremblay , J , Tönjes , A , van der Most , P J , Vitart , V , Völker , U , Wang , Y X , Wang , C , Wei , W B , Whitfield , J B , Wild , S H , Wilson , J F , Winkler , T W , Wong , T Y , Woodward , M , Sim , X , Chu , A Y , Feitosa , M F , Þorsteinsdóttir , U , Hung , A M , Teumer , A , Franceschini , N , Parsa , A , Köttgen , A , Schlosser , P & Pattaro , C 2024 , ' 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 ' , Nature Communications , vol. 15 , no. 1 , 586 , pp. 586 . https://doi.org/10.1038/s41467-024-44709-1
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Útdráttur: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.
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Athugasemdir:Publisher Copyright: © 2024, The Author(s). © 2024. The Author(s).
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