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

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

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 si...

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Veröffentlicht in:Nature Communications 2024-01, Vol.15 (1)
Hauptverfasser: Scholz, M., Horn, K., Wuttke, M., Kirsten, H., Li, Y., Hoppmann, A., Gorski, M., Li, M., Tin, A., Cocca, M., Wang, J., Nutile, T., Akiyama, M., Bansal, N., Biggs, M.L., Boutin, T., Brenner, H., Brumpton, B., Cai, J.W., Campbell, A., Chalmers, J., Chasman, D., Chen, X., Daviglus, M., Delgado, G., Edwards, T.L., Endlich, K., Gaziano, J.M., Hallan, S., Hamet, P., Holleczek, B., Holm, H., Hutri-Kähönen, N., Hveem, K., Isermann, B., Jonas, J.B., Kamatani, Y., Kastarinen, M., Khor, C.C., Kiess, W., Körner, A., Krajcoviechova, A., Kramer, H., Krämer, B.K., Kuokkanen, M., Kähönen, M., Lash, J.P., Lehtimäki, T., Li, H.T., Lin, B.M., Loeffler, M., Magnusson, P.K.E., Martin, N.G., Matsuda, K., Mishra, P.P., Mook-Kanamori, D.O., Mychaleckyj, J.C., März, W., Nikus, K., Noordam, R., Okada, Y., Oldehinkel, A.J., Penninx, B.W.J.H., Perola, M., Porteous, D.J., Rabelink, T.J., Raffield, L.M., Rasheed, H., Reilly, D.F., Rice, K.M., Richmond, A., Ridker, P.M., Rotter, J., Rudan, I., Sabanayagam, C., Salomaa, V., Snieder, H., Stark, K.J., Stefansson, K., Stocker, H., Stumvoll, M., Sulem, P., Svensson, P.O., Tham, Y.C., Thiery, J., Thio, C.H.L., Thomas, L.F., Tönjes, A., Vitart, V., Völker, U., Wang, Y.X., Wang, C.L., Wei, W.B., Wild, S.H., Woodward, M., Sim, X., Feitosa, M.F., Hung, A.M., Parsa, A., Schlosser, P.
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Sprache:eng
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Zusammenfassung: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.
DOI:10.1038/s41467-024-44709-1