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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.
Thursday,2024-02-01 20:41 America/Los_Angeles — ecterry
| Title | 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. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| Authors | Scholz, M, Horn, K, Pott, J, Wuttke, M, Kühnapfel, A, M Nasr, 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, BOlav, Bansal, N, Biggs, ML, Boutin, T, Brenner, H, Brumpton, B, Burkhardt, R, Cai, J, Campbell, A, Campbell, H, Chalmers, J, Chasman, DI, Chee, MLing, Chee, MLi, Chen, X, Cheng, C-Y, Cifkova, R, Daviglus, M, Delgado, G, Dittrich, K, Edwards, TL, Endlich, K, J Gaziano, M, Giri, A, Giulianini, F, Gordon, SD, Gudbjartsson, DF, Hallan, S, Hamet, P, Hartman, CA, Hayward, C, Heid, IM, Hellwege, JN, Holleczek, B, Holm, H, Hutri-Kähönen, N, Hveem, K, Isermann, B, Jonas, JB, Joshi, PK, Kamatani, Y, Kanai, M, Kastarinen, M, Khor, CChuen, Kiess, W, Kleber, ME, Körner, A, Kovacs, P, Krajcoviechova, A, Kramer, H, Krämer, BK, Kuokkanen, M, Kähönen, M, Lange, LA, Lash, JP, Lehtimäki, T, Li, H, Lin, BM, Liu, J, Loeffler, M, Lyytikäinen, L-P, Magnusson, PKE, Martin, NG, Matsuda, K, Milaneschi, Y, Mishra, PP, Mononen, N, Montgomery, GW, Mook-Kanamori, DO, Mychaleckyj, JC, März, W, Nauck, M, Nikus, K, Nolte, IM, Noordam, R, Okada, Y, Olafsson, I, Oldehinkel, AJ, Penninx, BWJH, Perola, M, Pirastu, N, Polasek, O, Porteous, DJ, Poulain, T, Psaty, BM, Rabelink, TJ, Raffield, LM, Raitakari, OT, Rasheed, H, Reilly, DF, Rice, KM, Richmond, A, Ridker, PM, Rotter, JI, Rudan, I, Sabanayagam, C, Salomaa, V, Schneiderman, N, Schöttker, B, Sims, M, Snieder, H, Stark, KJ, Stefansson, K, Stocker, H, Stumvoll, M, Sulem, P, Sveinbjornsson, G, Svensson, PO, Tai, E-S, Taylor, KD, Tayo, BO, Teren, A, Tham, Y-C, Thiery, J, Thio, CHL, Thomas, LF, Tremblay, J, Tönjes, A, van der Most, PJ, Vitart, V, Völker, U, Wang, YXing, Wang, C, Bin Wei, W, Whitfield, JB, Wild, SH, Wilson, JF, Winkler, TW, Wong, T-Y, Woodward, M, Sim, X, Chu, AY, Feitosa, MF, Thorsteinsdottir, U, Hung, AM, Teumer, A, Franceschini, N, Parsa, A, Köttgen, A, Schlosser, P, Pattaro, C |
| Journal | Nat Commun |
| Volume | 15 |
| Issue | 1 |
| Pagination | 586 |
| Date Published | 2024 Jan 18 |
| ISSN | 2041-1723 |
| Keywords | Androgens, Chromosomes, Human, X, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney, Male, Polymorphism, Single Nucleotide, Response Elements, Tetraspanins |
| Abstract | <p>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.</p> |
| DOI | 10.1038/s41467-024-44709-1 |
| Alternate Journal | Nat Commun |
| PubMed ID | 38233393 |
| PubMed Central ID | PMC10794254 |
ePub date:
24/01