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
JF ,
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
CY ,
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
LP ,
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
ES ,
Taylor
KD ,
Tayo
BO ,
Teren
A ,
Tham
YC ,
Thiery
J ,
Thio
CHL ,
Thomas
LF ,
Tremblay
J ,
Tönjes
A ,
van der Most
PJ ,
Vitart
V ,
Völker
U ,
Wang
YX ,
Wang
C ,
Wei
WB ,
Whitfield
JB ,
Wild
SH ,
Wilson
JF ,
Winkler
TW ,
Wong
TY ,
Woodward
M ,
Sim
X ,
Chu
AY ,
Feitosa
MF ,
Thorsteinsdottir
U ,
Hung
AM ,
Teumer
A ,
Franceschini
N ,
Parsa
A ,
Köttgen
A ,
Schlosser
P ,
Pattaro
C ,
. Nature communications. 2024 1 18; 15(1). 586
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.