Using Penalised Logistic Regression to Fine Map HLA Variants for Rheumatoid Arthritis
Charlotte M Vignal, Aruna T Bansal, David J Balding
Annals of Human Genetics | WILEY | Published : 2011
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-expone..View full abstract
Special thanks are due to the participants in our study. The authors would also like to thank Mike Binks (GlaxoSmithKline UK), Marion Dickson (GlaxoSmithKline UK), Doug Montgomery (GlaxoSmithKline UK) and Gerry Wilson (University of Sheffield) for their support, as well as Clive Hoggart (Imperial College London) for help with implementation of the HyperLASSO.