PMID- 21883133
OWN - NLM
STAT- MEDLINE
DCOM- 20111129
LR  - 20111006
IS  - 1469-1809 (Electronic)
IS  - 0003-4800 (Linking)
VI  - 75
IP  - 6
DP  - 2011 Nov
TI  - Using penalised logistic regression to fine map HLA variants for rheumatoid 
      arthritis.
PG  - 655-64
LID - 10.1111/j.1469-1809.2011.00670.x [doi]
AB  - Rheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen 
      (HLA) genomic region, most notably with a group of HLA-DRB1 alleles termed the 
      shared epitope (SE). There is also substantial evidence of other risk loci in the 
      HLA region, but refinement has been hampered by extensive linkage disequilibrium 
      (LD). Using genotype imputation, we analysed 6575 RA cases and controls with 
      genotypes at 6180 HLA SNPs; about half the subjects had four-digit DRB1 
      genotypes. Single-SNP tests revealed hundreds of strong associations across the 
      HLA region, even after adjusting for DRB1. We implemented penalised logistic 
      regression in a multi-SNP association analysis using the double-exponential (DE) 
      penalty term on the regression coefficients and the normal-exponential-gamma 
      (NEG). The penalised approaches identified sparse sets of SNPs that could 
      collectively explain most of the association with RA over the whole HLA region. 
      The HLA-DPB1 SNP rs3117225, was consistently identified in our analyses and was 
      confirmed by results from the North American Rheumatoid Arthritis Consortium 
      study (NARAC). We conclude that SNP selection using penalised regression shows a 
      substantial benefit over single-SNP analyses in identifying risk loci in regions 
      of high LD, and the flexibility of the NEG conveys additional advantages.
CI  - (c) 2011 The Authors Annals of Human Genetics (c) 2011 Blackwell Publishing 
      Ltd/University College London.
FAU - Vignal, Charlotte M
AU  - Vignal CM
AD  - Department of Epidemiology and Public Health, Imperial College London, UK.
FAU - Bansal, Aruna T
AU  - Bansal AT
FAU - Balding, David J
AU  - Balding DJ
LA  - eng
PT  - Journal Article
DEP - 20110901
PL  - England
TA  - Ann Hum Genet
JT  - Annals of human genetics
JID - 0416661
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPB1 antigen)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Arthritis, Rheumatoid/*genetics
MH  - Case-Control Studies
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-DP beta-Chains/genetics
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Humans
MH  - *Logistic Models
MH  - *Polymorphism, Single Nucleotide
EDAT- 2011/09/03 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/09/03 06:00
PHST- 2011/09/03 06:00 [entrez]
PHST- 2011/09/03 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1111/j.1469-1809.2011.00670.x [doi]
PST - ppublish
SO  - Ann Hum Genet. 2011 Nov;75(6):655-64. doi: 10.1111/j.1469-1809.2011.00670.x. Epub 
      2011 Sep 1.