期刊
HUMAN GENETICS
卷 133, 期 8, 页码 985-995出版社
SPRINGER
DOI: 10.1007/s00439-014-1439-z
关键词
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资金
- National Institutes of Health (NIH)/National Heart Lung and Blood Institute (NHLBI) [HHSN268200625226C]
- 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]
- NINDS
- NIA [AG-023629, AG-15928, AG-20098, AG-027058, AG08122, AG033193]
- National Institute on Minority Health and Health Disparities [N01 HC-95170, N01 HC-95171, N01 HC-95172]
- German Research Center for Environmental Health, Neuherberg, Germany
- German Federal Ministry of Education and Research
- German National Genome Research Network [01GS0834]
- German Research Foundation [TH-784/2-1, TH-784/2-2]
- European Foundation
- Helmholtz Zentrum Munchen
- German Diabetes Center
- University of Ulm
- Munich Center of Health Sciences as part of the Ludwig Maximilians University innovative
- National Heart, Lung, and Blood Institute (NHLBI) [CD36 rs3211938]
- 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]
- 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]
- [N01 HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [RR-024156]
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.
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