Association of CDKN2A/CDKN2B with inﬂammatory bowel
disease in Koreans
Soo Bin Lee,*
Byoung Mok Kim,* Myunghee Hong,* Seulgi Jung,* Jeonghoon Hong,*
Jiwon Baek,* Buhm Han,
Seak Hee Oh,
Kyung Mo Kim,
Sang Hyoung Park,
Byong Duk Ye
and Kyuyoung Song*
*Department of Biochemistry and Molecular Biology,
Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Institute for
Department of Pediatrics, Asan Medical Center Children’s Hospital, and
Department of Gastroenterology, Asan Medical Center, University
of Ulsan College of Medicine, Seoul, Korea
CDKN2A/CDKN2B, genetics, inﬂammatory
bowel disease, Korea, risk loci.
Accepted for publication 16 October 2017.
Dr Byong Duk Ye, Department of
Gastroenterology, Asan Medical Center,
University of Ulsan College of Medicine, 88
Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.
Dr Kyuyoung Song, Department of Biochemistry
and Molecular Biology, University of Ulsan
College of Medicine, 88 Olympic-ro 43-gil,
Songpa-gu, Seoul 05505, Korea.
These authors contributed to this work equally.
These authors jointly directed this work.
Declaration of conflict of interest: The authors
disclose the following: Byong Duk Ye: lecture
fees for Abbvie Korea, Janssen Korea Ltd,
CELLTRION, Inc., and Takeda Korea; consultant
for Shire Korea, Abbvie Korea, Kuhnil Pharm.,
CELLTRION, Inc., Takeda Korea, Kangstem
Biotech, Robarts Clinical Trials Inc., and Quintiles.
Suk-Kyun Yang: grant/research support from
Janssen Korea Ltd. The remaining authors have
no conﬂicts of interest to declare.
Financial support: This work was supported by a
Korean Health Technology R&D Project grant
from the Korea Health Industry Development
Institute to S.-K. Yang (A120176), funded by the
Ministry of Health & Welfare, as well as a Mid-
Career Researcher Program grant from the
National Research Foundation of Korea to
Background and Aim: CDKN2A/CDKN2B locus on 9p21 is reported to be associated
with various diseases, including cancer and cardiovascular and inﬂammatory diseases. Sig-
niﬁcant downregulation of CDKN2B-AS1 in inﬂamed colon tissue of inﬂammatory bowel
disease (IBD) cases was reported in Europeans. This study aimed to conﬁrm the suggestive
association of CDKN2A/CDKN2B with IBD identiﬁed in our recent genome-wide associa-
tion study (GWAS).
Methods: We examined the association of CDKN2A/CDKN2B locus with IBD in an addi-
tional sample of 574 IBD cases and 542 controls, totaling 4068 cases and 8074 controls. In
silico study was performed at various levels for functional annotation of the causal variant.
Co-localization of the GWAS association signals and the corresponding expression quan-
titative trait loci in IBD-related tissues was evaluated using eCAVIAR.
Results: An expanded GWAS showed genome-wide signiﬁcant association of rs3731257
at 9p21 with IBD (odds ratio = 1.17, 95% conﬁdence interval = 1.12–1.22,
= 5.68 × 10
) and Crohn’s disease (odds ratio = 1.22, 95% conﬁdence inter-
val = 1.15–1.28, P
= 8.85 × 10
) in the Korean population. Co-localization study
suggested that both CDKN2B-AS1 and CDKN2A might be functionally associated with the
locus in the small intestine.
Conclusions: rs3731257 in CDKN2A/CDKN2B is an IBD-susceptible locus in Koreans,
with a suggestive role for small intestine-speciﬁc gene regulation. Our ﬁndings suggested
that alterations of the CDKN2A/CDKN2B locus could affect the pathophysiology of IBD.
K. Song (2017R1A2A1A05001119), funded by the Ministry of Science, Information & Communication
Technology, and Future Planning of the Republic of Korea. Biospecimens and data for this study
were provided from the Korean Genome Analysis Project (4845-301), Korean Genome and
Epidemiology Study (4845-302), and Korea Biobank Project (4851-307, KBP-2015-000), which were
supported by the Korea Centers for Disease Control & Prevention, Republic of Korea. This work
was supported by the PLSI supercomputing resources of the Korea Institute of Science and
Inﬂammatory bowel disease (IBD) is characterized by chronic in-
ﬂammation in the gastrointestinal tract, presumably due to dysregu-
lation of the microbial ﬂora in genetically susceptible individuals.
Recent large-scale genome-wide association studies (GWASs) in
populations of the European ancestry advanced our understanding
of IBD-related genetics by identifying over 241 susceptibility loci
However, the known variants only account for a fraction
of IBD heritability. Despite differences in the clinical characteristics
Journal of Gastroenterology and Hepatology 33 (2018) 887–893
© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd