PuSH - Publikationsserver des Helmholtz Zentrums München: Large multiethnic candidate gene study for C-reactive protein levels: Identification of a novel association at <em>CD36</em> in African Americans.

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Ellis, J.* ; Lange, E.M.* ; Li, J.* ; Dupuis, J.* ; Baumert, J.J. ; Walston, J.D.* ; Keating, B.J.* ; Durda, P.* ; Fox, E.R.* ; Palmer, C.D.* ; Meng, Y.A.* ; Young, T.* ; Farlow, D.N.* ; Schnabel, R.B.* ; Marzi, C. ; Larkin, E.* ; Martin, L.W.* ; Bis, J.C.* ; Auer, P.* ; Ramachandran, V.S.* ; Gabriel, S.B.* ; Willis, M.S.* ; Pankow, J.S.* ; Papanicolau, G.J.* ; Rotter, J.I.* ; Ballantyne, C.M.* ; Gross, M.D.* ; Lettre, G.* ; Wilson, J.G.* ; Peters, U.* ; Koenig, W.* ; Tracy, R.P.* ; Redline, S.* ; Reiner, A.P.* ; Benjamin, E.J.* ; Lange, L.A.*

Large multiethnic candidate gene study for C-reactive protein levels: Identification of a novel association at CD36 in African Americans.

Hum. Genet. 133, 985-995 (2014)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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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