PMID- 29773854
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20191220
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 May 17
TI  - Genome-wide haplotype association analysis of primary biliary cholangitis risk in 
      Japanese.
PG  - 7806
LID - 10.1038/s41598-018-26112-1 [doi]
LID - 7806
AB  - Primary biliary cholangitis (PBC) susceptibility loci have largely been 
      discovered through single SNP association testing. In this study, we report genic 
      haplotype patterns associated with PBC risk genome-wide in two Japanese cohorts. 
      Among the 74 genic PBC risk haplotype candidates we detected with a novel 
      methodological approach in a discovery cohort of 1,937 Japanese, nearly 
      two-thirds were replicated (49 haplotypes, Bonferroni-corrected P < 6.8 x 10(-4)) 
      in an independent Japanese cohort (N = 949). Along with corroborating known 
      PBC-associated loci (TNFSF15, HLA-DRA), risk haplotypes may potentially model 
      cis-interactions that regulate gene expression. For example, one replicated 
      haplotype association (9q32-9q33.1, OR = 1.7, P = 3.0 x 10(-21)) consists of 
      intergenic SNPs outside of the human leukocyte antigen (HLA) region that overlap 
      regulatory histone mark peaks in liver and blood cells, and are significantly 
      associated with TNFSF8 expression in whole blood. We also replicated a novel 
      haplotype association involving non-HLA SNPs mapped to UMAD1 (7p21.3; OR = 15.2, 
      P = 3.9 x 10(-9)) that overlap enhancer peaks in liver and memory T(h) cells. Our 
      analysis demonstrates the utility of haplotype association analyses in 
      discovering and characterizing PBC susceptibility loci.
FAU - Im, Cindy
AU  - Im C
AD  - School of Public Health, University of Alberta, Edmonton, Alberta, T6G 1C9, 
      Canada. cim1@ualberta.ca.
FAU - Sapkota, Yadav
AU  - Sapkota Y
AD  - Department of Epidemiology and Cancer Control, St. Jude Children's Research 
      Hospital, Memphis, TN, 38105, USA.
FAU - Moon, Wonjong
AU  - Moon W
AD  - Department of Epidemiology and Cancer Control, St. Jude Children's Research 
      Hospital, Memphis, TN, 38105, USA.
FAU - Kawashima, Minae
AU  - Kawashima M
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, 113-0033, Japan.
FAU - Nakamura, Minoru
AU  - Nakamura M
AD  - Department of Hepatology, Nagasaki University Graduate School of Biomedical 
      Sciences and Clinical Research Center, National Hospital Organization Nagasaki 
      Medical Center, Omura, Nagasaki, 856-8562, Japan.
FAU - Tokunaga, Katsushi
AU  - Tokunaga K
AD  - Department of Human Genetics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, 113-0033, Japan.
FAU - Yasui, Yutaka
AU  - Yasui Y
AD  - School of Public Health, University of Alberta, Edmonton, Alberta, T6G 1C9, 
      Canada. yutaka.yasui@stjude.org.
AD  - Department of Epidemiology and Cancer Control, St. Jude Children's Research 
      Hospital, Memphis, TN, 38105, USA. yutaka.yasui@stjude.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180517
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
MH  - Cohort Studies
MH  - Computational Biology
MH  - Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - Haplotypes
MH  - Humans
MH  - Japan/epidemiology
MH  - Liver Cirrhosis, Biliary/epidemiology/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
PMC - PMC5958065
COIS- The authors declare no competing interests.
EDAT- 2018/05/19 06:00
MHDA- 2019/12/21 06:00
PMCR- 2018/05/17
CRDT- 2018/05/19 06:00
PHST- 2018/01/16 00:00 [received]
PHST- 2018/04/30 00:00 [accepted]
PHST- 2018/05/19 06:00 [entrez]
PHST- 2018/05/19 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2018/05/17 00:00 [pmc-release]
AID - 10.1038/s41598-018-26112-1 [pii]
AID - 26112 [pii]
AID - 10.1038/s41598-018-26112-1 [doi]
PST - epublish
SO  - Sci Rep. 2018 May 17;8(1):7806. doi: 10.1038/s41598-018-26112-1.