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

TitleRheumatoid Arthritis and Coronary Artery Disease: Genetic Analyses Do Not Support a Causal Relation.
Publication TypeJournal Article
Year of Publication2017
AuthorsJansen H, Willenborg C, Lieb W, Zeng L, Ferrario PGloria, Loley C, König IR, Erdmann J, Samani NJ
Secondary AuthorsSchunkert H
Corporate AuthorsCARDIoGRAM Consortium
JournalJ Rheumatol
Date Published2017 01
KeywordsAlleles, Arthritis, Rheumatoid, Cholesterol, LDL, Coronary Artery Disease, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide

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

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.

Alternate JournalJ Rheumatol
PubMed ID27744395
Grant ListR01 HL087698 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
M01 RR000052 / RR / NCRR NIH HHS / United States
U01 HL072518 / HL / NHLBI NIH HHS / United States
R01 HL112064 / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States