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- Title
Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.
- Authors
Ellis, Jaclyn; Lange, Ethan; Li, Jin; Dupuis, Josee; Baumert, Jens; Walston, Jeremy; Keating, Brendan; Durda, Peter; Fox, Ervin; Palmer, Cameron; Meng, Yan; Young, Taylor; Farlow, Deborah; Schnabel, Renate; Marzi, Carola; Larkin, Emma; Martin, Lisa; Bis, Joshua; Auer, Paul; Ramachandran, Vasan
- Abstract
C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multiethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7,570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women's Health Initiative (WHI) and KORA studies. We observed array-wide significance ( p < 2.2 × 10) for four loci in AA, three of which have been reported previously in individuals of European descent ( IL6R, p = 2.0 × 10; CRP, p = 4.2 × 10; APOE, p = 1.6 × 10). The fourth significant locus, CD36 ( p = 1.6 × 10), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding ( p = 1.8 × 10) in an independent sample of 8,041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance ( p = 1.5 × 10). In the race-combined meta-analyses, 13 loci reached significance, including ten ( CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one ( ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected ( RPS6KB1, p = 2.0 × 10; CD36, p = 1.4 × 10). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent.
- Subjects
C-reactive protein; CARDIOVASCULAR diseases; MEDICAL genetics; ACUTE phase proteins; GENETICS of race
- Publication
Human Genetics, 2014, Vol 133, Issue 8, p985
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-014-1439-z