%0 Journal Article %J Hum Genet %D 2014 %T Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans. %A Ellis, Jaclyn %A Lange, Ethan M %A Li, Jin %A Dupuis, Josée %A Baumert, Jens %A Walston, Jeremy D %A Keating, Brendan J %A Durda, Peter %A Fox, Ervin R %A Palmer, Cameron D %A Meng, Yan A %A Young, Taylor %A Farlow, Deborah N %A Schnabel, Renate B %A Marzi, Carola S %A Larkin, Emma %A Martin, Lisa W %A Bis, Joshua C %A Auer, Paul %A Ramachandran, Vasan S %A Gabriel, Stacey B %A Willis, Monte S %A Pankow, James S %A Papanicolaou, George J %A Rotter, Jerome I %A Ballantyne, Christie M %A Gross, Myron D %A Lettre, Guillaume %A Wilson, James G %A Peters, Ulrike %A Koenig, Wolfgang %A Tracy, Russell P %A Redline, Susan %A Reiner, Alex P %A Benjamin, Emelia J %A Lange, Leslie A %K Adult %K African Americans %K Aged %K Biomarkers %K C-Reactive Protein %K Cardiovascular Diseases %K CD36 Antigens %K Female %K Genetic Loci %K Genetic Predisposition to Disease %K Genetics, Population %K Genome-Wide Association Study %K Humans %K Meta-Analysis as Topic %K Middle Aged %K Polymorphism, Single Nucleotide %K Risk Factors %X

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(-6)) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p = 2.0 × 10(-6); CRP, p = 4.2 × 10(-71); APOE, p = 1.6 × 10(-6)). The fourth significant locus, CD36 (p = 1.6 × 10(-6)), 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(-5)) 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(-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(-6); CD36, p = 1.4 × 10(-6)). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent.

%B Hum Genet %V 133 %P 985-95 %8 2014 Aug %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/24643644?dopt=Abstract %R 10.1007/s00439-014-1439-z