alexa Autosome-wide copy number variation association analysis for rheumatoid arthritis using the WTCCC high-density SNP genotype data.
Mathematics

Mathematics

Journal of Biometrics & Biostatistics

Author(s): Uddin M, Sturge M, Rahman P, Woods MO

Abstract Share this page

Abstract OBJECTIVE: Rheumatoid arthritis (RA) is a complex autoimmune rheumatic disease that is strongly influenced by genetic factors. Numerous genes are convincingly associated with RA, including genes in tumor necrosis factor signaling (TNF) and the nuclear factor-κB pathway. To date, except for genes within the HLA region, no data exist regarding potential copy number variations (CNV) involving RA-associated genes. We set out to identify genes affected by CNV that are associated with RA at a genome-wide level. METHODS: Data from the Wellcome Trust Case Control Consortium (WTCCC) were used in our analyses. The initial WTCCC cohort genotyped 3004 controls and 1999 RA cases using the GeneChip 500k Mapping Array Set. We performed a comparative intensity analysis using the PennCNV algorithm, which uses a hidden Markov model to detect CNV. A total of 2271 controls and 1572 RA samples passed quality control criteria and were included for association analysis. Association analysis was performed in 2 phases: (1) to identify CNV that are < 1 Mb with a population frequency < 5\%; and (2) to identify large CNV that are > 1 Mb. Fishers' exact test was performed to quantify significance of the CNV. RESULTS: We observed that the genome-wide CNV burden is 2-fold higher in patients with RA compared with controls. We identified 11 rare copy number variable regions with < 5\% frequency that had an association with RA that reached a p < 1 × 10(-4). These include TNFAIP3 and TNIP1, which has been implicated in association studies for RA, systemic lupus erythematosus, and psoriasis. We identified CNV involving IRF1, which functions as a transcription activator of genes induced by interferons; ALOX5AP and LCP2, involved in inflammatory mediation; B2M, an MHC-class I associated gene; and PRKCH, a gene involved in T cell signaling pathways. A 57 kb deletion with 1\% frequency in RA cases at 7p21.3 was also observed. Six of these loci overlap with CNV catalogued in the Database of Genomic Variants. CONCLUSION: This is the first study to identify non-HLA RA-associated CNV using genome-wide analyses. Validation and functional significance of these deletions/duplications in RA and other autoimmune diseases need to be further investigated. This article was published in J Rheumatol and referenced in Journal of Biometrics & Biostatistics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]ine.com

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords