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

  • Author(s): 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
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104766/
No data is associated with this publication.
Abstract

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.

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