You are here
Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.
Wednesday,2015-03-04 12:20 America/Los_Angeles — zdrager
| Title | Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Ellis, 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 |
| Journal | Hum Genet |
| Volume | 133 |
| Issue | 8 |
| Pagination | 985-95 |
| Date Published | 2014 Aug |
| ISSN | 1432-1203 |
| Keywords | Adult, 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> |
| DOI | 10.1007/s00439-014-1439-z |
| Alternate Journal | Hum. Genet. |
| PubMed ID | 24643644 |
| PubMed Central ID | PMC4104766 |
| Grant List | N01-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 |