Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans
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Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans. / Ellis, Jaclyn; Lange, Ethan M; Li, Jin; Dupuis, Josee; Baumert, Jens; Walston, Jeremy D; Keating, Brendan J; Durda, Peter; Fox, Ervin R; Palmer, Cameron D; Meng, Yan A; Young, Taylor; Farlow, Deborah N; Schnabel, Renate B; Marzi, Carola S; Larkin, Emma; Martin, Lisa W; Bis, Joshua C; Auer, Paul; Ramachandran, Vasan S; Gabriel, Stacey B; Willis, Monte S; Pankow, James S; Papanicolaou, George J; Rotter, Jerome I; Ballantyne, Christie M; Gross, Myron D; Lettre, Guillaume; Wilson, James G; Peters, Ulrike; Koenig, Wolfgang; Tracy, Russell P; Redline, Susan; Reiner, Alex P; Benjamin, Emelia J; Lange, Leslie A.
In: HUM GENET, Vol. 133, No. 8, 08.2014, p. 985-995.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans
AU - Ellis, Jaclyn
AU - Lange, Ethan M
AU - Li, Jin
AU - Dupuis, Josee
AU - Baumert, Jens
AU - Walston, Jeremy D
AU - Keating, Brendan J
AU - Durda, Peter
AU - Fox, Ervin R
AU - Palmer, Cameron D
AU - Meng, Yan A
AU - Young, Taylor
AU - Farlow, Deborah N
AU - Schnabel, Renate B
AU - Marzi, Carola S
AU - Larkin, Emma
AU - Martin, Lisa W
AU - Bis, Joshua C
AU - Auer, Paul
AU - Ramachandran, Vasan S
AU - Gabriel, Stacey B
AU - Willis, Monte S
AU - Pankow, James S
AU - Papanicolaou, George J
AU - Rotter, Jerome I
AU - Ballantyne, Christie M
AU - Gross, Myron D
AU - Lettre, Guillaume
AU - Wilson, James G
AU - Peters, Ulrike
AU - Koenig, Wolfgang
AU - Tracy, Russell P
AU - Redline, Susan
AU - Reiner, Alex P
AU - Benjamin, Emelia J
AU - Lange, Leslie A
PY - 2014/8
Y1 - 2014/8
N2 - 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.
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.
KW - Adult
KW - African Americans/genetics
KW - Aged
KW - Biomarkers/analysis
KW - C-Reactive Protein/metabolism
KW - CD36 Antigens/genetics
KW - Cardiovascular Diseases/etiology
KW - Female
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genetics, Population
KW - Genome-Wide Association Study
KW - Humans
KW - Meta-Analysis as Topic
KW - Middle Aged
KW - Polymorphism, Single Nucleotide/genetics
KW - Risk Factors
U2 - 10.1007/s00439-014-1439-z
DO - 10.1007/s00439-014-1439-z
M3 - SCORING: Journal article
C2 - 24643644
VL - 133
SP - 985
EP - 995
JO - HUM GENET
JF - HUM GENET
SN - 0340-6717
IS - 8
ER -