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Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.

TitleLarge multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.
Publication TypeJournal Article
Year of Publication2014
AuthorsEllis, J, Lange, EM, Li, J, Dupuis, J, Baumert, J, Walston, JD, Keating, BJ, Durda, P, Fox, ER, Palmer, CD, Meng, YA, Young, T, Farlow, DN, Schnabel, RB, Marzi, CS, Larkin, E, Martin, LW, Bis, JC, Auer, P, Ramachandran, VS, Gabriel, SB, Willis, MS, Pankow, JS, Papanicolaou, GJ, Rotter, JI, Ballantyne, CM, Gross, MD, Lettre, G, Wilson, JG, Peters, U, Koenig, W, Tracy, RP, Redline, S, Reiner, AP, Benjamin, EJ, Lange, LA
JournalHum Genet
Volume133
Issue8
Pagination985-95
Date Published2014 Aug
ISSN1432-1203
KeywordsAdult, African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, CD36 Antigens, Female, Genetic Loci, Genetic Predisposition to Disease, Genetics, Population, Genome-Wide Association Study, Humans, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors
Abstract<p>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.</p>
DOI10.1007/s00439-014-1439-z
Alternate JournalHum. Genet.
PubMed ID24643644
PubMed Central IDPMC4104766
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
N01-HC48049 / HC / NHLBI NIH HHS / United States
N01-HC48050 / HC / NHLBI NIH HHS / United States
N01 HC-95171 / HC / NHLBI NIH HHS / United States
N01 HC-55015 / HC / NHLBI NIH HHS / United States
N01 HC-55021 / HC / NHLBI NIH HHS / United States
RC2 HL-102926 / HL / NHLBI NIH HHS / United States
N01 HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC48048 / HC / NHLBI NIH HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
N01-HC-95168 / HC / NHLBI NIH HHS / United States
R01 NS17950 / NS / NINDS NIH HHS / United States
RC2 HL-102923 / HL / NHLBI NIH HHS / United States
AG033193 / AG / NIA NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
N01-HC-95165 / HC / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
AG08122 / AG / NIA NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
N01 HC-55020 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
RC2 HL-102924 / HL / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01HC-55017 / HC / NHLBI NIH HHS / United States
N01-HC48047 / HC / NHLBI NIH HHS / United States
N01 HC-95159 / HC / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
N01-HC-95164 / HC / NHLBI NIH HHS / United States
N01 HC-95172 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
R01 HL071862 / HL / NHLBI NIH HHS / United States
N01-HC-95160 / HC / NHLBI NIH HHS / United States
RC2 HL-102925 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01-HC-95161 / HC / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
AG-023629 / AG / NIA NIH HHS / United States
N01-HC-95166 / HC / NHLBI NIH HHS / United States
RC2 HL-103010 / HL / NHLBI NIH HHS / United States
N01 HC-95170 / HC / NHLBI NIH HHS / United States
N01-HC95095 / HC / NHLBI NIH HHS / United States
N01-HC-95167 / HC / NHLBI NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States
N01 HC-55019 / HC / NHLBI NIH HHS / United States