PMID- 28721485
OWN - NLM
STAT- MEDLINE
DCOM- 20180620
LR  - 20221207
IS  - 1573-7373 (Electronic)
IS  - 0167-594X (Print)
IS  - 0167-594X (Linking)
VI  - 135
IP  - 2
DP  - 2017 Nov
TI  - Non-additive and epistatic effects of HLA polymorphisms contributing to risk of 
      adult glioma.
PG  - 237-244
LID - 10.1007/s11060-017-2569-7 [doi]
AB  - Although genome-wide association studies have identified several susceptibility 
      loci for adult glioma, little is known regarding the potential contribution of 
      genetic variation in the human leukocyte antigen (HLA) region to glioma risk. HLA 
      associations have been reported for various malignancies, with many studies 
      investigating selected candidate HLA polymorphisms. However, no systematic 
      analysis has been conducted in glioma patients, and no investigation into 
      potential non-additive effects has been described. We conducted comprehensive 
      genetic analyses of HLA variants among 1746 adult glioma patients and 2312 
      controls of European-ancestry from the GliomaScan Consortium. Genotype data were 
      generated with the Illumina 660-Quad array, and we imputed HLA alleles using a 
      reference panel of 5225 individuals in the Type 1 Diabetes Genetics Consortium 
      who underwent high-resolution HLA typing via next-generation sequencing. 
      Case-control comparisons were adjusted for population stratification using 
      ancestry-informative principal components. Because alleles in different loci 
      across the HLA region are linked, we created multigene haplotypes consisting of 
      the genes DRB1, DQA1, and DQB1. Although none of the haplotypes were associated 
      with glioma in additive models, inclusion of a dominance term significantly 
      improved the model for multigene haplotype HLA-DRB1*1501-DQA1*0102-DQB1*0602 
      (P = 0.002). Heterozygous carriers of the haplotype had an increased risk of 
      glioma [odds ratio (OR) 1.23; 95% confidence interval (CI) 1.01-1.49], while 
      homozygous carriers were at decreased risk compared with non-carriers (OR 0.64; 
      95% CI 0.40-1.01). Our results suggest that the DRB1*1501-DQA1*0102-DQB1*0602 
      haplotype may contribute to the risk of glioma in a non-additive manner, with the 
      positive dominance effect partly explained by an epistatic interaction with 
      HLA-DRB1*0401-DQA1*0301-DQB1*0301.
FAU - Zhang, Chenan
AU  - Zhang C
AUID- ORCID: 0000-0003-1773-4441
AD  - Division of Neuroepidemiology, Department of Neurological Surgery, University of 
      California, San Francisco, San Francisco, CA, 94158, USA. Chenan.Zhang@ucsf.edu.
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, San Francisco, CA, 94158, USA. Chenan.Zhang@ucsf.edu.
FAU - de Smith, Adam J
AU  - de Smith AJ
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, San Francisco, CA, 94158, USA.
FAU - Smirnov, Ivan V
AU  - Smirnov IV
AD  - Division of Neuroepidemiology, Department of Neurological Surgery, University of 
      California, San Francisco, San Francisco, CA, 94158, USA.
FAU - Wiencke, John K
AU  - Wiencke JK
AD  - Division of Neuroepidemiology, Department of Neurological Surgery, University of 
      California, San Francisco, San Francisco, CA, 94158, USA.
FAU - Wiemels, Joseph L
AU  - Wiemels JL
AD  - Division of Neuroepidemiology, Department of Neurological Surgery, University of 
      California, San Francisco, San Francisco, CA, 94158, USA.
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, San Francisco, CA, 94158, USA.
FAU - Witte, John S
AU  - Witte JS
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, San Francisco, CA, 94158, USA.
FAU - Walsh, Kyle M
AU  - Walsh KM
AD  - Division of Neuroepidemiology, Department of Neurological Surgery, University of 
      California, San Francisco, San Francisco, CA, 94158, USA.
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, San Francisco, CA, 94158, USA.
AD  - Division of Neuro-epidemiology, Department of Neurosurgery, Duke University, 
      Durham, NC, 27710, USA.
LA  - eng
GR  - T32 CA151022/CA/NCI NIH HHS/United States
GR  - R25 CA112355/CA/NCI NIH HHS/United States
GR  - U01 DK062418/DK/NIDDK NIH HHS/United States
GR  - R01 CA207360/CA/NCI NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - N01CO12400/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170718
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Brain Neoplasms/*genetics
MH  - Case-Control Studies
MH  - Female
MH  - Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - Glioma/*genetics
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Models, Genetic
MH  - Polymorphism, Single Nucleotide
MH  - White People/genetics
PMC - PMC5665694
MID - NIHMS893893
OTO - NOTNLM
OT  - Brain tumor
OT  - Epistasis
OT  - Glioma
OT  - HLA
OT  - Interactions
OT  - MHC
OT  - Non-additive effects
COIS- Conflict of Interest: The authors declare that they have no conflict of interest.
EDAT- 2017/07/20 06:00
MHDA- 2018/06/21 06:00
PMCR- 2018/11/01
CRDT- 2017/07/20 06:00
PHST- 2017/04/20 00:00 [received]
PHST- 2017/07/13 00:00 [accepted]
PHST- 2017/07/20 06:00 [pubmed]
PHST- 2018/06/21 06:00 [medline]
PHST- 2017/07/20 06:00 [entrez]
PHST- 2018/11/01 00:00 [pmc-release]
AID - 10.1007/s11060-017-2569-7 [pii]
AID - 10.1007/s11060-017-2569-7 [doi]
PST - ppublish
SO  - J Neurooncol. 2017 Nov;135(2):237-244. doi: 10.1007/s11060-017-2569-7. Epub 2017 
      Jul 18.