title: Identification of correlated genetic variants jointly associated with rheumatoid arthritis using ridge regression.
abstract: 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.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory, Ann Arbor, Michigan 48109, USA.
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
authors.affiliation: Department of Statistics, University of Michigan, 439 West Hall, 1085 South University, Ann Arbor, Michigan 48109, USA.
authors.forename: Kerby A
authors.initials: KA
authors.lastname: Shedden
authors.affiliation: Department of Statistics, University of Michigan, 439 West Hall, 1085 South University, Ann Arbor, Michigan 48109, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Statistics, University of Michigan, 439 West Hall, 1085 South University, Ann Arbor, Michigan 48109, USA.
authors.forename: Nam-Hee
authors.initials: NH
authors.lastname: Choi
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory, Ann Arbor, Michigan 48109, USA.
authors.forename: Sharon Lr
authors.initials: SL
authors.lastname: Kardia