Classification of rheumatoid arthritis status with candidate gene and genome-wide single-nucleotide polymorphisms using random forests.
Using the North American Rheumatoid Arthritis Consortium (NARAC) candidate gene and genome-wide single-nucleotide polymorphism (SNP) data sets, we applied regression methods and tree-based random forests to identify genetic associations with rheumatoid arthritis (RA) and to predict RA disease status. Several genes were consistently identified as weakly associated with RA without a significant interaction or combinatorial effect with other candidate genes. Using random forests, the tested candidate gene SNPs were not sufficient to predict RA patients and normal subjects with high accuracy. However, using the top 500 SNPs, ranked by the importance score, from the genome-wide linkage panel of 5742 SNPs, we were able to accurately predict RA patients and normal subjects with sensitivity of approximately 90% and specificity of approximately 80%, which was confirmed by five-fold cross-validation. However, in a complete training-testing framework, replication of genetic predictors was less satisfactory; thus, further evaluation of existing methodology and development of new methods are warranted.
Sun
Yan V
YV
Department of Epidemiology, School of Public Health, University of Michigan, 611 Church Street #244, Ann Arbor, Michigan 48104, USA.
Cai
Zhaohui
Z
AstraZeneca Pharmaceuticals, 1800 Concord Place, FOC W1-462, Wilmington, Delaware 19850, USA.
Desai
Kaushal
K
AstraZeneca Pharmaceuticals, 1800 Concord Place, FOC W1-462, Wilmington, Delaware 19850, USA.
Lawrance
Rachael
R
AstraZeneca Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
Leff
Richard
R
AstraZeneca Pharmaceuticals, 1800 Concord Place, FOC W1-462, Wilmington, Delaware 19850, USA.
Jawaid
Ansar
A
AstraZeneca Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
Kardia
Sharon Lr
SL
Department of Epidemiology, School of Public Health, University of Michigan, 611 Church Street #244, Ann Arbor, Michigan 48104, USA.
Yang
Huiying
H
AstraZeneca Pharmaceuticals, 1800 Concord Place, FOC W1-462, Wilmington, Delaware 19850, USA.