4.6 Article

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

Journal

HUMAN GENETICS
Volume 133, Issue 8, Pages 985-995

Publisher

SPRINGER
DOI: 10.1007/s00439-014-1439-z

Keywords

-

Funding

  1. National Institutes of Health (NIH)/National Heart Lung and Blood Institute (NHLBI) [HHSN268200625226C]
  2. NHLBI [N01 HC-55015, N01 HC-55016, N01HC-55017, N01 HC-55018, N01 HC-55019, N01 HC-55020, N01 HC-55021, N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083]
  3. NINDS
  4. NIA [AG-023629, AG-15928, AG-20098, AG-027058, AG08122, AG033193]
  5. National Institute on Minority Health and Health Disparities [N01 HC-95170, N01 HC-95171, N01 HC-95172]
  6. German Research Center for Environmental Health, Neuherberg, Germany
  7. German Federal Ministry of Education and Research
  8. German National Genome Research Network [01GS0834]
  9. German Research Foundation [TH-784/2-1, TH-784/2-2]
  10. European Foundation
  11. Helmholtz Zentrum Munchen
  12. German Diabetes Center
  13. University of Ulm
  14. Munich Center of Health Sciences as part of the Ludwig Maximilians University innovative
  15. National Heart, Lung, and Blood Institute (NHLBI) [CD36 rs3211938]
  16. NHLBI. [N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HHSN268201200036C]
  17. The NHLBI [N01-HC95095, N01-HC48047, N01-HC48048, N01-HC48049, N01-HC48050, N01-HC-25195, R01 NS17950, N01-HC-65226, R01 HL071862, RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2 HL-102926]
  18. [N01 HC-95159]
  19. [N01-HC-95160]
  20. [N01-HC-95161]
  21. [N01-HC-95162]
  22. [N01-HC-95163]
  23. [N01-HC-95164]
  24. [N01-HC-95165]
  25. [N01-HC-95166]
  26. [N01-HC-95167]
  27. [N01-HC-95168]
  28. [N01-HC-95169]
  29. [RR-024156]

Ask authors/readers for more resources

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 x 10(-6)) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p = 2.0 x 10(-6); CRP, p = 4.2 x 10(-71); APOE, p = 1.6 x 10(-6)). The fourth significant locus, CD36 (p = 1.6 x 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 x 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 x 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 x 10(-6); CD36, p = 1.4 x 10(-6)). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available