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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.

SUBMITTER: Sun YV 

PROVIDER: S-EPMC2795968 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Identification of correlated genetic variants jointly associated with rheumatoid arthritis using ridge regression.

Sun Yan V YV   Shedden Kerby A KA   Zhu Ji J   Choi Nam-Hee NH   Kardia Sharon Lr SL  

BMC proceedings 20091215


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  ...[more]

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