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

Scholz M; Horn K; Pott J; Wuttke M; Kühnapfel A; Nasr MK; Kirsten H; Li Y; Hoppmann A; Gorski M; Ghasemi S; Li M; Tin A; Chai J; Cocca M; Wang J; Nutile T; Akiyama M; Åsvold BO; Bansal N; Biggs ML; Boutin T; Brenner H; Brumpton B; Burkhardt R; Cai J; Campbell A; Campbell H; Chalmers J; Chasman DI; Chee ML; Chee ML; Chen X; Cheng C; Cifkova R; Daviglus M; Delgado G; Dittrich K; Edwards TL; Endlich K; Michael Gaziano J; 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 CC; 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; 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; Taylor KD; Tayo BO; Teren A; Tham Y; Thiery J; Thio CHL; Thomas LF; Tremblay J; Tönjes A; Most PJ; Vitart V; Völker U; Wang YX; Wang C; Wei WB; Whitfield JB; Wild SH; Wilson JF; Winkler TW; Wong T; Woodward M; Sim X; Chu AY; Feitosa MF; Thorsteinsdottir U; Hung AM; 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

Scholz M; Horn K; Pott J; Wuttke M; Kühnapfel A; Nasr MK; Kirsten H; Li Y; Hoppmann A; Gorski M; Ghasemi S; Li M; Tin A; Chai J; Cocca M; Wang J; Nutile T; Akiyama M; Åsvold BO; Bansal N; Biggs ML; Boutin T; Brenner H; Brumpton B; Burkhardt R; Cai J; Campbell A; Campbell H; Chalmers J; Chasman DI; Chee ML; Chee ML; Chen X; Cheng C; Cifkova R; Daviglus M; Delgado G; Dittrich K; Edwards TL; Endlich K; Michael Gaziano J; 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 CC; 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; 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; Taylor KD; Tayo BO; Teren A; Tham Y; Thiery J; Thio CHL; Thomas LF; Tremblay J; Tönjes A; Most PJ; Vitart V; Völker U; Wang YX; Wang C; Wei WB; Whitfield JB; Wild SH; Wilson JF; Winkler TW; Wong T; Woodward M; Sim X; Chu AY; Feitosa MF; Thorsteinsdottir U; Hung AM; 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

Scholz M

Horn K

Pott J

Wuttke M

Kühnapfel A

Nasr MK

Kirsten H

Li Y

Hoppmann A

Gorski M

Ghasemi S

Li M

Tin A

Chai J

Cocca M

Wang J

Nutile T

Akiyama M

Åsvold BO

Bansal N

Biggs ML

Boutin T

Brenner H

Brumpton B

Burkhardt R

Cai J

Campbell A

Campbell H

Chalmers J

Chasman DI

Chee ML

Chen X

Cheng C

Cifkova R

Daviglus M

Delgado G

Dittrich K

Edwards TL

Endlich K

Michael Gaziano J

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 CC

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

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

Taylor KD

Tayo BO

Teren A

Tham Y

Thiery J

Thio CHL

Thomas LF

Tremblay J

Tönjes A

Most PJ

Vitart V

Völker U

Wang YX

Wang C

Wei WB

Whitfield JB

Wild SH

Wilson JF

Winkler TW

Wong T

Woodward M

Sim X

Chu AY

Feitosa MF

Thorsteinsdottir U

Hung AM

Teumer A

Franceschini N

Parsa A

Köttgen A

Schlosser P

Pattaro C

Katso/Avaa

s41467-024-44709-1.pdf (4.204Mb)

Lataukset:

Nature Research

doi:10.1038/s41467-024-44709-1

URI

https://www.nature.com/articles/s41467-024-44709-1

Näytä kaikki kuvailutiedot

Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2025082792327

Tiivistelmä

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. © 2024, The Author(s).

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