TY - JOUR
AU - Lange,  Leslie
AB - 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.
TI - Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans
JF - Human Genetics
DO - 10.1007/s00439-014-1439-z
DA - 2014-08-01
UR - https://www.deepdyve.com/lp/springer-journals/large-multiethnic-candidate-gene-study-for-c-reactive-protein-levels-121z31sfPJ
SP - 985
EP - 995
VL - 133
IS - 8
DP - DeepDyve
ER -