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

Almenn færsla
dc.contributor.authorScholz, Markus
dc.contributor.authorHorn, Katrin
dc.contributor.authorPott, Janne
dc.contributor.authorWuttke, Matthias
dc.contributor.authorKühnapfel, Andreas
dc.contributor.authorNasr, M. Kamal
dc.contributor.authorKirsten, Holger
dc.contributor.authorLi, Yong
dc.contributor.authorHoppmann, Anselm
dc.contributor.authorGorski, Mathias
dc.contributor.authorGhasemi, Sahar
dc.contributor.authorLi, Man
dc.contributor.authorTin, Adrienne
dc.contributor.authorChai, Jin Fang
dc.contributor.authorCocca, Massimiliano
dc.contributor.authorWang, Judy
dc.contributor.authorNutile, Teresa
dc.contributor.authorAkiyama, Masato
dc.contributor.authorÅsvold, Bjørn Olav
dc.contributor.authorBansal, Nisha
dc.contributor.authorBiggs, Mary L.
dc.contributor.authorBoutin, Thibaud
dc.contributor.authorBrenner, Hermann
dc.contributor.authorBrumpton, Ben
dc.contributor.authorBurkhardt, Ralph
dc.contributor.authorCai, Jianwen
dc.contributor.authorCampbell, Archie
dc.contributor.authorCampbell, Harry
dc.contributor.authorChalmers, John
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorChee, Miao Ling
dc.contributor.authorChee, Miao Li
dc.contributor.authorChen, Xu
dc.contributor.authorCheng, Ching Yu
dc.contributor.authorCifkova, Renata
dc.contributor.authorDaviglus, Martha
dc.contributor.authorDelgado, Graciela
dc.contributor.authorDittrich, Katalin
dc.contributor.authorEdwards, Todd L.
dc.contributor.authorEndlich, Karlhans
dc.contributor.authorMichael Gaziano, J.
dc.contributor.authorGiri, Ayush
dc.contributor.authorGiulianini, Franco
dc.contributor.authorGordon, Scott D.
dc.contributor.authorGudbjartsson, Daniel F.
dc.contributor.authorHallan, Stein
dc.contributor.authorHamet, Pavel
dc.contributor.authorHartman, Catharina A.
dc.contributor.authorHayward, Caroline
dc.contributor.authorHeid, Iris M.
dc.contributor.authorHellwege, Jacklyn N.
dc.contributor.authorHolleczek, Bernd
dc.contributor.authorHolm, Hilma
dc.contributor.authorHutri-Kähönen, Nina
dc.contributor.authorHveem, Kristian
dc.contributor.authorIsermann, Berend
dc.contributor.authorJonas, Jost B.
dc.contributor.authorJoshi, Peter K.
dc.contributor.authorKamatani, Yoichiro
dc.contributor.authorKanai, Masahiro
dc.contributor.authorKastarinen, Mika
dc.contributor.authorKhor, Chiea Chuen
dc.contributor.authorKiess, Wieland
dc.contributor.authorKleber, Marcus E.
dc.contributor.authorKörner, Antje
dc.contributor.authorKovacs, Peter
dc.contributor.authorKrajcoviechova, Alena
dc.contributor.authorKramer, Holly
dc.contributor.authorKrämer, Bernhard K.
dc.contributor.authorKuokkanen, Mikko
dc.contributor.authorKähönen, Mika
dc.contributor.authorLange, Leslie A.
dc.contributor.authorLash, James P.
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorLi, Hengtong
dc.contributor.authorLin, Bridget M.
dc.contributor.authorLiu, Jianjun
dc.contributor.authorLoeffler, Markus
dc.contributor.authorLyytikäinen, Leo Pekka
dc.contributor.authorMagnusson, Patrik K.E.
dc.contributor.authorMartin, Nicholas G.
dc.contributor.authorMatsuda, Koichi
dc.contributor.authorMilaneschi, Yuri
dc.contributor.authorMishra, Pashupati P.
dc.contributor.authorMononen, Nina
dc.contributor.authorMontgomery, Grant W.
dc.contributor.authorMook-Kanamori, Dennis O.
dc.contributor.authorMychaleckyj, Josyf C.
dc.contributor.authorMärz, Winfried
dc.contributor.authorNauck, Matthias
dc.contributor.authorNikus, Kjell
dc.contributor.authorNolte, Ilja M.
dc.contributor.authorNoordam, Raymond
dc.contributor.authorOkada, Yukinori
dc.contributor.authorÓlafsson, Ísleifur
dc.contributor.authorOldehinkel, Albertine J.
dc.contributor.authorPenninx, Brenda W.J.H.
dc.contributor.authorPerola, Markus
dc.contributor.authorPirastu, Nicola
dc.contributor.authorPolasek, Ozren
dc.contributor.authorPorteous, David J.
dc.contributor.authorPoulain, Tanja
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorRabelink, Ton J.
dc.contributor.authorRaffield, Laura M.
dc.contributor.authorRaitakari, Olli T.
dc.contributor.authorRasheed, Humaira
dc.contributor.authorReilly, Dermot F.
dc.contributor.authorRice, Kenneth M.
dc.contributor.authorRichmond, Anne
dc.contributor.authorRidker, Paul M.
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorRudan, Igor
dc.contributor.authorSabanayagam, Charumathi
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorSchneiderman, Neil
dc.contributor.authorSchöttker, Ben
dc.contributor.authorSims, Mario
dc.contributor.authorSnieder, Harold
dc.contributor.authorStark, Klaus J.
dc.contributor.authorStefánsson, Kári
dc.contributor.authorStocker, Hannah
dc.contributor.authorStumvoll, Michael
dc.contributor.authorSulem, Patrick
dc.contributor.authorSveinbjornsson, Gardar
dc.contributor.authorSvensson, Per O.
dc.contributor.authorTai, E. Shyong
dc.contributor.authorTaylor, Kent D.
dc.contributor.authorTayo, Bamidele O.
dc.contributor.authorTeren, Andrej
dc.contributor.authorTham, Yih Chung
dc.contributor.authorThiery, Joachim
dc.contributor.authorThio, Chris H.L.
dc.contributor.authorThomas, Laurent F.
dc.contributor.authorTremblay, Johanne
dc.contributor.authorTönjes, Anke
dc.contributor.authorvan der Most, Peter J.
dc.contributor.authorVitart, Veronique
dc.contributor.authorVölker, Uwe
dc.contributor.authorWang, Ya Xing
dc.contributor.authorWang, Chaolong
dc.contributor.authorWei, Wen Bin
dc.contributor.authorWhitfield, John B.
dc.contributor.authorWild, Sarah H.
dc.contributor.authorWilson, James F.
dc.contributor.authorWinkler, Thomas W.
dc.contributor.authorWong, Tien Yin
dc.contributor.authorWoodward, Mark
dc.contributor.authorSim, Xueling
dc.contributor.authorChu, Audrey Y.
dc.contributor.authorFeitosa, Mary F.
dc.contributor.authorÞorsteinsdóttir, Unnur
dc.contributor.authorHung, Adriana M.
dc.contributor.authorTeumer, Alexander
dc.contributor.authorFranceschini, Nora
dc.contributor.authorParsa, Afshin
dc.contributor.authorKöttgen, Anna
dc.contributor.authorSchlosser, Pascal
dc.contributor.authorPattaro, Cristian
dc.contributor.departmentFaculty of Medicine
dc.contributor.schoolHealth Sciences
dc.date.accessioned2025-11-20T09:30:52Z
dc.date.available2025-11-20T09:30:52Z
dc.date.issued2024-01-18
dc.descriptionPublisher Copyright: © 2024, The Author(s). © 2024. The Author(s).en
dc.description.abstractX-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.en
dc.description.versionPeer revieweden
dc.format.extent4409238
dc.format.extent586
dc.identifier.citationScholz, 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/s41467-024-44709-1en
dc.identifier.doi10.1038/s41467-024-44709-1
dc.identifier.issn2041-1723
dc.identifier.other216623577
dc.identifier.otherd4a3b1a4-339d-4354-8e02-b2ce77c221dc
dc.identifier.other85182684565
dc.identifier.other38233393
dc.identifier.otherunpaywall: 10.1038/s41467-024-44709-1
dc.identifier.urihttps://hdl.handle.net/20.500.11815/7463
dc.language.isoen
dc.relation.ispartofseriesNature Communications; 15(1)en
dc.relation.urlhttps://www.scopus.com/pages/publications/85182684565en
dc.rightsinfo:eu-repo/semantics/openAccessen
dc.subjectHumansen
dc.subjectMaleen
dc.subjectFemaleen
dc.subjectAndrogens/geneticsen
dc.subjectGenome-Wide Association Studyen
dc.subjectKidneyen
dc.subjectChromosomes, Human, X/geneticsen
dc.subjectResponse Elementsen
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectTetraspanins/geneticsen
dc.subjectGeneral Chemistryen
dc.subjectGeneral Biochemistry,Genetics and Molecular Biologyen
dc.subjectGeneral Physics and Astronomyen
dc.titleX-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 elementsen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/articleen

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