Abstract
Original language | English |
---|---|
Article number | 586 |
Journal | Nature communications |
Volume | 15 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Dec 2024 |
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In: Nature communications, Vol. 15, No. 1, 586, 01.12.2024.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - X-chromosome and kidney function
T2 - 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
AU - Scholz, Markus
AU - Horn, Katrin
AU - Pott, Janne
AU - Wuttke, Matthias
AU - Kühnapfel, Andreas
AU - Nasr, M. Kamal
AU - Kirsten, Holger
AU - Li, Yong
AU - Hoppmann, Anselm
AU - Gorski, Mathias
AU - Ghasemi, Sahar
AU - Li, Man
AU - Tin, Adrienne
AU - Chai, Jin-Fang
AU - Cocca, Massimiliano
AU - Wang, Judy
AU - Nutile, Teresa
AU - Akiyama, Masato
AU - Åsvold, Bjørn Olav
AU - Bansal, Nisha
AU - Biggs, Mary L.
AU - Boutin, Thibaud
AU - Brenner, Hermann
AU - Brumpton, Ben
AU - Burkhardt, Ralph
AU - Cai, Jianwen
AU - Campbell, Archie
AU - Campbell, Harry
AU - Chalmers, John
AU - Chasman, Daniel I.
AU - Chee, Miao Ling
AU - Chee, Miao Li
AU - Chen, Xu
AU - Cheng, Ching-Yu
AU - Cifkova, Renata
AU - Daviglus, Martha
AU - Delgado, Graciela
AU - Dittrich, Katalin
AU - Edwards, Todd L.
AU - Endlich, Karlhans
AU - Michael Gaziano, J.
AU - Giri, Ayush
AU - Giulianini, Franco
AU - Gordon, Scott D.
AU - Gudbjartsson, Daniel F.
AU - Hallan, Stein
AU - Hamet, Pavel
AU - Hartman, Catharina A.
AU - Hayward, Caroline
AU - Heid, Iris M.
AU - Hellwege, Jacklyn N.
AU - Holleczek, Bernd
AU - Holm, Hilma
AU - Hutri-Kähönen, Nina
AU - Hveem, Kristian
AU - Isermann, Berend
AU - Jonas, Jost B.
AU - Joshi, Peter K.
AU - Kamatani, Yoichiro
AU - Kanai, Masahiro
AU - Kastarinen, Mika
AU - Khor, Chiea Chuen
AU - Kiess, Wieland
AU - Kleber, Marcus E.
AU - Körner, Antje
AU - Kovacs, Peter
AU - Krajcoviechova, Alena
AU - Kramer, Holly
AU - Krämer, Bernhard K.
AU - Kuokkanen, Mikko
AU - Kähönen, Mika
AU - Lange, Leslie A.
AU - Lash, James P.
AU - Lehtimäki, Terho
AU - Li, Hengtong
AU - Lin, Bridget M.
AU - Liu, Jianjun
AU - Loeffler, Markus
AU - Lyytikäinen, Leo-Pekka
AU - Magnusson, Patrik K. E.
AU - Martin, Nicholas G.
AU - Matsuda, Koichi
AU - Milaneschi, Yuri
AU - Mishra, Pashupati P.
AU - Mononen, Nina
AU - Montgomery, Grant W.
AU - Mook-Kanamori, Dennis O.
AU - Mychaleckyj, Josyf C.
AU - März, Winfried
AU - Nauck, Matthias
AU - Nikus, Kjell
AU - Nolte, Ilja M.
AU - Noordam, Raymond
AU - Okada, Yukinori
AU - Olafsson, Isleifur
AU - Oldehinkel, Albertine J.
AU - Penninx, Brenda W. J. H.
AU - Perola, Markus
AU - Pirastu, Nicola
AU - Polasek, Ozren
AU - Porteous, David J.
AU - Poulain, Tanja
AU - Psaty, Bruce M.
AU - Rabelink, Ton J.
AU - Raffield, Laura M.
AU - Raitakari, Olli T.
AU - Rasheed, Humaira
AU - Reilly, Dermot F.
AU - Rice, Kenneth M.
AU - Richmond, Anne
AU - Ridker, Paul M.
AU - Rotter, Jerome I.
AU - Rudan, Igor
AU - Sabanayagam, Charumathi
AU - Salomaa, Veikko
AU - Schneiderman, Neil
AU - Schöttker, Ben
AU - Sims, Mario
AU - Snieder, Harold
AU - Stark, Klaus J.
AU - Stefansson, Kari
AU - Stocker, Hannah
AU - Stumvoll, Michael
AU - Sulem, Patrick
AU - Sveinbjornsson, Gardar
AU - Svensson, Per O.
AU - Tai, E. Shyong
AU - Taylor, Kent D.
AU - Tayo, Bamidele O.
AU - Teren, Andrej
AU - Tham, Yih-Chung
AU - Thiery, Joachim
AU - Thio, Chris H. L.
AU - Thomas, Laurent F.
AU - Tremblay, Johanne
AU - Tönjes, Anke
AU - van der Most, Peter J.
AU - Vitart, Veronique
AU - Völker, Uwe
AU - Wang, Ya Xing
AU - Wang, Chaolong
AU - Wei, Wen Bin
AU - Whitfield, John B.
AU - Wild, Sarah H.
AU - Wilson, James F.
AU - Winkler, Thomas W.
AU - Wong, Tien-Yin
AU - Woodward, Mark
AU - Sim, Xueling
AU - Chu, Audrey Y.
AU - Feitosa, Mary F.
AU - Thorsteinsdottir, Unnur
AU - Hung, Adriana M.
AU - Teumer, Alexander
AU - Franceschini, Nora
AU - Parsa, Afshin
AU - Köttgen, Anna
AU - Schlosser, Pascal
AU - Pattaro, Cristian
N1 - Publisher Copyright: © 2024, The Author(s).
PY - 2024/12/1
Y1 - 2024/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85182684565&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-44709-1
DO - 10.1038/s41467-024-44709-1
M3 - Article
C2 - 38233393
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 586
ER -