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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.* ; 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.* ; Olafsson, I.* ; 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.* ; Stefansson, 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.* ; Thorsteinsdottir, U.* ; Hung, A.M.* ; Teumer, A.* ; Franceschini, N.* ; Parsa, A.* ; Köttgen, A.* ; Schlosser, P.* ; Pattaro, C.*

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.

Nat. Commun. 15:586 (2024)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Disease; Men; Testosterone; Discovery; Binding; Issues
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 15, Issue: 1, Pages: , Article Number: 586 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-506503-001
Grants German Research Foundation (DFG)
German Federal Ministry of Education and Research (BMBF)
DOI 10.1038/s41467-024-44709-1
WOS ID 001187887400001
Scopus ID 85182684565
PubMed ID 38233393
Erfassungsdatum 2024-01-22
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