Identification of correlated genetic variants jointly associated with rheumatoid arthritis using ridge regression.
Using the North American Rheumatoid Arthritis Consortium genome-wide association dataset, we applied ridged, multiple least-squares regression to identify genetic variants with apparent unique contributions to variation of anti-cyclic citrullinated peptide (anti-CCP), a newly identified clinical risk factor for development of rheumatoid arthritis. Within a 2.7-Mbp region on chromosome 6 around the well studied HLA-DRB1 locus, ridge regression identified a single-nucleotide polymorphism that was associated with anti-CCP variation when including the additive effects of other single-nucleotide polymorphisms in a multivariable analysis, but that showed only a weak direct association with anti-CCP. This suggests that multivariable methods can be used to identify potentially relevant genetic variants in regions of interest that would be difficult to detect based on direct associations.
Sun
Yan V
YV
Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory, Ann Arbor, Michigan 48109, USA.
Shedden
Kerby A
KA
Department of Statistics, University of Michigan, 439 West Hall, 1085 South University, Ann Arbor, Michigan 48109, USA.
Zhu
Ji
J
Department of Statistics, University of Michigan, 439 West Hall, 1085 South University, Ann Arbor, Michigan 48109, USA.
Choi
Nam-Hee
NH
Department of Statistics, University of Michigan, 439 West Hall, 1085 South University, Ann Arbor, Michigan 48109, USA.
Kardia
Sharon Lr
SL
Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory, Ann Arbor, Michigan 48109, USA.