PMID- 26733291
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20221207
IS  - 1476-5438 (Electronic)
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 24
IP  - 7
DP  - 2016 Jul
TI  - Common coding variants in the HLA-DQB1 region confer susceptibility to 
      age-related macular degeneration.
PG  - 1049-55
LID - 10.1038/ejhg.2015.247 [doi]
AB  - Age-related macular degeneration (AMD) risk variants in the complement system 
      point to the important role of immune response and inflammation in the 
      pathogenesis of AMD. Although the human leukocyte antigen (HLA) region has a 
      central role in regulating immune response, previous studies of genetic variation 
      in HLA genes and AMD have been limited by sample size or incomplete coverage of 
      the HLA region by first-generation genotyping arrays and imputation panels. Here, 
      we conducted a large-scale HLA fine-mapping study with 4841 AMD cases and 23 790 
      controls of non-Hispanic white ancestry from the Kaiser Permanente Genetic 
      Epidemiology Research on Adult Health and Aging cohort. Genotyping was conducted 
      using custom Affymetrix Axiom arrays, with dense coverage of the HLA region. 
      Classic HLA polymorphisms were imputed using SNP2HLA, which utilizes a large 
      reference panel to provide improved imputation accuracy of variants in this 
      region. We examined a total of 6937 SNPs and 172 classical HLA alleles, 
      conditioning on established AMD risk variants, which revealed novel associations 
      with two non-synonymous SNPs in perfect linkage disequilibrium, rs9274390 and 
      rs41563814 (odds ratio (OR)=1.21; P=1.4 x 10(-11)) corresponding to amino-acid 
      changes at position 66 and 67 in HLA-DQB1, respectively, and the DQB1*02 
      classical HLA allele (OR=1.22; P=3.9 x 10(-10)) with the risk of AMD. We 
      confirmed these association signals, again conditioning on established risk 
      variants, in the MMAP data set of subjects with advanced AMD 
      (rs9274390/rs41563814: OR=1.28; P=1.30 x 10(-3), DQB1*02: OR=1.32; P=9.00 x 
      10(-4)). These findings support a role of HLA class II alleles in the risk of 
      AMD.
FAU - Jorgenson, Eric
AU  - Jorgenson E
AD  - Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.
FAU - Melles, Ronald B
AU  - Melles RB
AD  - Department of Ophthalmology, Kaiser Permanente Northern California Redwood City 
      Medical Center, Redwood City, CA, USA.
FAU - Hoffmann, Thomas J
AU  - Hoffmann TJ
AD  - Institute for Human Genetics, University of California-San Francisco, San 
      Francisco, CA, USA.
AD  - Department of Epidemiology and Biostatistics, University of California-San 
      Francisco, San Francisco, CA, USA.
FAU - Jia, Xiaoming
AU  - Jia X
AD  - Department of Neurology, University of California-San Francisco, San Francisco, 
      CA, USA.
FAU - Sakoda, Lori C
AU  - Sakoda LC
AD  - Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.
FAU - Kvale, Mark N
AU  - Kvale MN
AD  - Institute for Human Genetics, University of California-San Francisco, San 
      Francisco, CA, USA.
FAU - Banda, Yambazi
AU  - Banda Y
AD  - Institute for Human Genetics, University of California-San Francisco, San 
      Francisco, CA, USA.
FAU - Schaefer, Catherine
AU  - Schaefer C
AD  - Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.
FAU - Risch, Neil
AU  - Risch N
AD  - Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.
AD  - Institute for Human Genetics, University of California-San Francisco, San 
      Francisco, CA, USA.
AD  - Department of Epidemiology and Biostatistics, University of California-San 
      Francisco, San Francisco, CA, USA.
FAU - Shen, Ling
AU  - Shen L
AD  - Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.
LA  - eng
GR  - R21 AA021223/AA/NIAAA NIH HHS/United States
GR  - R21 AG046616/AG/NIA NIH HHS/United States
GR  - RC2 AG036607/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20160106
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Case-Control Studies
MH  - Female
MH  - HLA-DQ beta-Chains/*genetics
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Macular Degeneration/*genetics/pathology
MH  - Male
MH  - *Mutation, Missense
MH  - *Polymorphism, Single Nucleotide
MH  - White People/genetics
PMC - PMC5070898
EDAT- 2016/01/07 06:00
MHDA- 2017/07/27 06:00
PMCR- 2017/07/01
CRDT- 2016/01/07 06:00
PHST- 2015/03/25 00:00 [received]
PHST- 2015/09/21 00:00 [revised]
PHST- 2015/10/15 00:00 [accepted]
PHST- 2016/01/07 06:00 [entrez]
PHST- 2016/01/07 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - ejhg2015247 [pii]
AID - 10.1038/ejhg.2015.247 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2016 Jul;24(7):1049-55. doi: 10.1038/ejhg.2015.247. Epub 2016 
      Jan 6.