PMID- 23053058
OWN - NLM
STAT- MEDLINE
DCOM- 20130222
LR  - 20211021
IS  - 1432-1211 (Electronic)
IS  - 0093-7711 (Linking)
VI  - 65
IP  - 1
DP  - 2013 Jan
TI  - Search for schizophrenia susceptibility variants at the HLA-DRB1 locus among a 
      British population.
PG  - 1-7
LID - 10.1007/s00251-012-0652-y [doi]
AB  - Schizophrenia is a complex mental disorder with unknown aetiology. Both candidate 
      gene and genome-wide association (GWA) studies suggest that the human leukocyte 
      antigen (HLA) system may play a part in development of the illness, but the 
      causal HLA variant(s) remain(s) unclear. Previous studies showed that the 
      DRB1*0101 and DRB1*13 alleles might be associated with a high risk of 
      schizophrenia. Therefore, the present study was undertaken to test their 
      association with the disease by genotyping seven DRB1-tagging single nucleotide 
      polymorphisms (SNPs) in a British population. The results showed that, of the 
      previously reported variants that were associated with schizophrenia, the 
      DRB1*1303 allele was the only one marginally associated with a protective effect 
      on the illness in our sample set (chi(2) = 4.138, P = 0.042, odds ratio (OR) = 0.42, 
      95 % confidence interval (CI) 0.27-0.66). Interestingly, a significant 
      association was found for rs424232 (chi(2) = 9.404, P = 0.002, OR = 0.69, 95 % CI 
      0.54-0.88), which is a tag SNP for the DRB1*1303 allele and located near to the 
      NOTCH4 gene that is a schizophrenia susceptibility locus confirmed by GWA 
      studies. Analysis with the Haploview program demonstrated that rs424232 was in 
      complete linkage disequilibrium with rs3130297 and rs3131296 present in the 
      NOTCH4 locus. While we have failed to confirm association of the candidate 
      alleles in the DRB1 gene with a high risk of schizophrenia, the present work 
      suggests that the association signal detected in the HLA class II locus may 
      extend a relatively long distance, and more work is needed in order to identify 
      the true causal variants within this region or nearby.
FAU - Halley, Lorna
AU  - Halley L
AD  - Department of Diabetes and Cardiovascular Science, Centre for Health Science, 
      University of the Highlands and Islands, Old Perth Road, Inverness IV2 3JH, UK.
FAU - Doherty, Mary K
AU  - Doherty MK
FAU - Megson, Ian L
AU  - Megson IL
FAU - McNamara, Neil
AU  - McNamara N
FAU - Gadja, Andy
AU  - Gadja A
FAU - Wei, Jun
AU  - Wei J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120929
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (NOTCH4 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptor, Notch4)
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Alleles
MH  - Base Sequence
MH  - Case-Control Studies
MH  - England
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - HLA-DRB1 Chains/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Proto-Oncogene Proteins/*genetics
MH  - Receptor, Notch4
MH  - Receptors, Notch/*genetics
MH  - Schizophrenia/*genetics
EDAT- 2012/10/12 06:00
MHDA- 2013/02/23 06:00
CRDT- 2012/10/12 06:00
PHST- 2012/06/07 00:00 [received]
PHST- 2012/09/10 00:00 [accepted]
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/02/23 06:00 [medline]
AID - 10.1007/s00251-012-0652-y [doi]
PST - ppublish
SO  - Immunogenetics. 2013 Jan;65(1):1-7. doi: 10.1007/s00251-012-0652-y. Epub 2012 Sep 
      29.