X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans.
OBJECTIVE
Genome-wide association studies of inflammatory bowel disease identified > 200 susceptibility loci only in autosomes. This study aimed to identify inflammatory bowel disease susceptibility loci on the X chromosome.


METHODS
We performed an X chromosome-wide association study in Korean patients with inflammatory bowel disease. We analysed X chromosome data from our recent genome-wide association studies, including 1505 cases [922 Crohn's disease and 583 ulcerative colitis] and 4041 controls during the discovery phase, followed by replication in additional 1989 cases [993 Crohn's disease, 996 ulcerative colitis] and 3491 controls. Sex-related differential effects of single nucleotide polymorphisms on disease were also evaluated.


RESULTS
We confirmed a significant association of a previously reported inflammatory bowel disease susceptibility locus at chromosome Xq26.3 [CD40LG-ARHGEF6; odds ratio, 1.22; 95% confidence interval, 1.16-1.28; combined p = 3.79 × 10-15]. This locus accounted for 0.18% and 0.12% of genetic variance in Crohn's disease and ulcerative colitis, respectively, and increased the total autosomal chromosome genetic variance from 6.65% to 6.83% and from 5.47% to 5.59% for Crohn's disease and ulcerative colitis risk, respectively, in the Korean population. Sex-stratified analyses did not reveal sex-related differences in effect sizes.


CONCLUSIONS
We confirmed the association of rs2427870 at the CD40LG-ARHGEF6 locus with an inflammatory bowel disease through an X chromosome-wide association study in a Korean population. Our data suggest that the CD40LG-ARHGEF6 locus on the X chromosome might play a role in inflammatory bowel disease pathogenesis in the Korean population.
Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea.|Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Ho-Su
HS
Lee
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Hyunjung
H
Oh
Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea.
Suk-Kyun
SK
Yang
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Jiwon
J
Baek
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Seulgi
S
Jung
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Myunghee
M
Hong
Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
Kyung Mo
KM
Kim
Department of Life Science, Sogang University, Seoul, Korea.
Hyoung Doo
HD
Shin
Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea.
Kyung-Jo
KJ
Kim
Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea.
Sang Hyoung
SH
Park
Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea.
Byong Duk
BD
Ye
Department of Convergence Medicine, University of Ulsan College of Medicine & Asan Institute for Life Sciences, Seoul, Korea.
Buhm
B
Han
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
Kyuyoung
K
Song
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D023201:CD40 Ligand / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics; D055815:Young Adult
C576603:ARHGEF6 protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; D023201:CD40 Ligand
CD40LG-ARHGEF6; X chromosome; inflammatory bowel disease