dc.contributor.author | Cui, Jing | en_US |
dc.contributor.author | Taylor, Kimberly E. | en_US |
dc.contributor.author | Lee, Yvonne C. | en_US |
dc.contributor.author | Källberg, Henrik | en_US |
dc.contributor.author | Weinblatt, Michael E. | en_US |
dc.contributor.author | Coblyn, Jonathan S. | en_US |
dc.contributor.author | Klareskog, Lars | en_US |
dc.contributor.author | Criswell, Lindsey A. | en_US |
dc.contributor.author | Gregersen, Peter K. | en_US |
dc.contributor.author | Shadick, Nancy A. | en_US |
dc.contributor.author | Plenge, Robert M. | en_US |
dc.contributor.author | Karlson, Elizabeth W. | en_US |
dc.date.accessioned | 2014-10-01T14:28:47Z | |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | Cui, J., K. E. Taylor, Y. C. Lee, H. Källberg, M. E. Weinblatt, J. S. Coblyn, L. Klareskog, et al. 2014. “The Influence of Polygenic Risk Scores on Heritability of Anti-CCP Level in RA.” Genes and immunity 15 (2): 107-114. doi:10.1038/gene.2013.68. http://dx.doi.org/10.1038/gene.2013.68. | en |
dc.identifier.issn | 1466-4879 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:12987317 | |
dc.description.abstract | Objective: To study genetic factors that influence quantitative anti-cyclic citrullinated peptide (anti-CCP) antibody levels in RA patients. Methods: We carried out a genome wide association study (GWAS) meta-analysis using 1,975 anti-CCP+ RA patients from 3 large cohorts, the Brigham Rheumatoid Arthritis Sequential Study (BRASS), North American Rheumatoid Arthritis Consortium (NARAC), and the Epidemiological Investigation of RA (EIRA). We also carried out a genome-wide complex trait analysis (GCTA) to estimate the heritability of anti-CCP levels. Results: GWAS-meta analysis showed that anti-CCP levels were most strongly associated with the human leukocyte antigen (HLA) region with a p-value of 2×10−11 for rs1980493. There were 112 SNPs in this region that exceeded the genome-wide significance threshold of 5×10−8, and all were in linkage disequilibrium (LD) with the HLA- DRB1*03 allele with LD r2 in the range of 0.25-0.88. Suggestive novel associations outside of the HLA region were also observed for rs8063248 (near the GP2 gene) with a p-value of 3×10−7. None of the known RA risk alleles (~52 loci) were associated with anti-CCP level. Heritability analysis estimated that 44% of anti-CCP variation was attributable to genetic factors captured by GWAS variants. Conclusions: Anti-CCP level is a heritable trait. HLA-DR3 and GP2 are associated with lower anti-CCP levels. | en |
dc.language.iso | en_US | en |
dc.relation.isversionof | doi:10.1038/gene.2013.68 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948067/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | RA | en |
dc.subject | GWAS | en |
dc.subject | anti-CCP | en |
dc.subject | heritability | en |
dc.title | The Influence of Polygenic Risk Scores on Heritability of Anti-CCP Level in RA | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Genes and immunity | en |
dash.depositing.author | Cui, Jing | en_US |
dc.date.available | 2014-10-01T14:28:47Z | |
dc.identifier.doi | 10.1038/gene.2013.68 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Cui, Jing | |
dash.contributor.affiliated | Lee, Yvonne Claire | |
dash.contributor.affiliated | Coblyn, Jonathan | |
dash.contributor.affiliated | Karlson, Elizabeth | |
dash.contributor.affiliated | Shadick, Nancy | |
dash.contributor.affiliated | Weinblatt, Michael | |