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

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dc.contributor.authorScholz M
dc.contributor.authorHorn K
dc.contributor.authorPott J
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dc.contributor.authorKühnapfel A
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dc.contributor.authorLi M
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dc.contributor.authorPoulain T
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dc.contributor.authorRabelink TJ
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dc.contributor.authorRaitakari OT
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dc.contributor.authorVitart V
dc.contributor.authorVölker U
dc.contributor.authorWang YX
dc.contributor.authorWang C
dc.contributor.authorWei WB
dc.contributor.authorWhitfield JB
dc.contributor.authorWild SH
dc.contributor.authorWilson JF
dc.contributor.authorWinkler TW
dc.contributor.authorWong T
dc.contributor.authorWoodward M
dc.contributor.authorSim X
dc.contributor.authorChu AY
dc.contributor.authorFeitosa MF
dc.contributor.authorThorsteinsdottir U
dc.contributor.authorHung AM
dc.contributor.authorTeumer A
dc.contributor.authorFranceschini N
dc.contributor.authorParsa A
dc.contributor.authorKöttgen A
dc.contributor.authorSchlosser P
dc.contributor.authorPattaro C
dc.contributor.organizationfi=InFLAMES Lippulaiva|en=InFLAMES Flagship|
dc.contributor.organizationfi=sydäntutkimuskeskus|en=Cardiovascular Medicine (CAPC)|
dc.contributor.organizationfi=tyks, vsshp|en=tyks, varha|
dc.contributor.organizationfi=väestötutkimuskeskus|en=Centre for Population Health Research (POP Centre)|
dc.contributor.organization-code1.2.246.10.2458963.20.35734063924
dc.contributor.organization-code1.2.246.10.2458963.20.42471027641
dc.contributor.organization-code1.2.246.10.2458963.20.68445910604
dc.converis.publication-id381279692
dc.converis.urlhttps://research.utu.fi/converis/portal/Publication/381279692
dc.date.accessioned2025-08-28T02:34:14Z
dc.date.available2025-08-28T02:34:14Z
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. © 2024, The Author(s).
dc.identifier.eissn2041-1723
dc.identifier.jour-issn2041-1723
dc.identifier.olddbid209320
dc.identifier.oldhandle10024/192347
dc.identifier.urihttps://www.utupub.fi/handle/11111/43165
dc.identifier.urlhttps://www.nature.com/articles/s41467-024-44709-1
dc.identifier.urnURN:NBN:fi-fe2025082792327
dc.language.isoen
dc.okm.affiliatedauthorRaitakari, Olli
dc.okm.affiliatedauthorDataimport, tyks, vsshp
dc.okm.discipline3121 Internal medicineen_GB
dc.okm.discipline318 Medical biotechnologyen_GB
dc.okm.discipline3121 Sisätauditfi_FI
dc.okm.discipline318 Lääketieteen bioteknologiafi_FI
dc.okm.internationalcopublicationinternational co-publication
dc.okm.internationalityInternational publication
dc.okm.typeA1 ScientificArticle
dc.publisherNature Research
dc.publisher.countryUnited Kingdomen_GB
dc.publisher.countryBritanniafi_FI
dc.publisher.country-codeGB
dc.relation.articlenumber586
dc.relation.doi10.1038/s41467-024-44709-1
dc.relation.ispartofjournalNature Communications
dc.relation.issue1
dc.relation.volume15
dc.source.identifierhttps://www.utupub.fi/handle/10024/192347
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 elements
dc.year.issued2024

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