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Rheumatoid Arthritis and Coronary Artery Disease: Genetic Analyses Do Not Support a Causal Relation.

Rheumatoid Arthritis and Coronary Artery Disease: Genetic Analyses Do Not Support a Causal Relation.
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Jansen H, Willenborg C, Lieb W, Zeng L, Ferrario PG, Loley C, König IR, Erdmann J, Samani NJ, Schunkert H, ,


Jansen H, Willenborg C, Lieb W, Zeng L, Ferrario PG, Loley C, König IR, Erdmann J, Samani NJ, Schunkert H, , (click to view)

Jansen H, Willenborg C, Lieb W, Zeng L, Ferrario PG, Loley C, König IR, Erdmann J, Samani NJ, Schunkert H, ,

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The Journal of rheumatology 2016 Oct 15() pii jrheum.151444
Abstract
OBJECTIVE
Inflammatory diseases, specifically rheumatoid arthritis (RA), are assumed to increase the risk of coronary artery disease (CAD). More recently, multiple single-nucleotide polymorphisms (SNP) associated with RA risk were identified. If causal mechanisms affecting risks of RA and CAD are overlapping, risk alleles for RA might also increase the risk of CAD.

METHODS
Sixty-one SNP associating with RA in genome-wide significant analyses were tested for association with CAD in CARDIoGRAM (Coronary ARtery DIsease Genome wide Replication and Meta-analysis), a metaanalysis including genome-wide association data (22,233 CAD cases, 64,762 controls). In parallel, a set of SNP being associated with low-density lipoprotein cholesterol (LDL-C) was tested as a positive control.

RESULTS
Twenty-nine RA-associated SNP displayed a directionality-consistent association with CAD (OR range 1.002-1.073), whereas 32 RA-associated SNP were not associated with CAD (OR range 0.96-0.99 per RA risk-increasing allele). The proportion (48%) of directionality-consistent associated SNP equaled the proportion expected by chance (50%, p = 0.09). Of only 5 RA-associated SNP showing p values for CAD < 0.05, 4 loci (C5orf30, IL-6R, PTPN22, and RAD51B) showed directionality-consistent effects on CAD, and 1 (rs10774624, locus SH2B3) reached study-wide significance (p = 7.29E-06). By contrast, and as a proof of concept, 46 (74%) out of 62 LDL-C-associated SNP displayed a directionality-consistent association with CAD, a proportion that was significantly different from 50% (p = 5.9E-05). CONCLUSION
We found no evidence that RA-associated SNP as a group are associated with CAD. Even though we were not able to study potential effects of all genetic variants individually, shared nongenetic factors may more plausibly explain the observed coincidence of the 2 conditions.

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