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A genetic association study of D-dimer levels with 50K SNPs from a candidate gene chip in four ethnic groups.
Wednesday,2015-03-04 14:21 America/Los_Angeles — zdrager
| Title | A genetic association study of D-dimer levels with 50K SNPs from a candidate gene chip in four ethnic groups. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Weng, L-C, Tang, W, Rich, SS, Smith, NL, Redline, S, O'Donnell, CJ, Basu, S, Reiner, AP, Delaney, JA, Tracy, RP, Palmer, CD, Young, T, Yang, Q, Folsom, AR, Cushman, M |
| Journal | Thromb Res |
| Volume | 134 |
| Issue | 2 |
| Pagination | 462-7 |
| Date Published | 2014 Aug |
| ISSN | 1879-2472 |
| Keywords | Adult, Aged, Cardiovascular Diseases, Ethnic Groups, Factor V, Female, Fibrin Fibrinogen Degradation Products, Fibrinogen, Genetic Association Studies, Genotype, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Young Adult |
| Abstract | <p><b>INTRODUCTION: </b>D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.</p><p><b>MATERIALS AND METHODS: </b>We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis.</p><p><b>RESULTS: </b>Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p<2.0×10(-6). The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p=0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p=0.006). No additional SNPs were significantly associated with D-dimer.</p><p><b>CONCLUSIONS: </b>Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.</p> |
| DOI | 10.1016/j.thromres.2014.05.018 |
| Alternate Journal | Thromb. Res. |
| PubMed ID | 24908450 |
| PubMed Central ID | PMC4111961 |
| Grant List | N01 HC-55222 / HC / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC065226 / HC / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States N01 HC085081 / HC / NHLBI NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States N01 HC085083 / HC / NHLBI NIH HHS / United States N01 HC085084 / HC / NHLBI NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States N01 HC095159 / HC / NHLBI NIH HHS / United States N01 HC095160 / HC / NHLBI NIH HHS / United States N01 HC095161 / HC / NHLBI NIH HHS / United States N01 HC095162 / HC / NHLBI NIH HHS / United States N01 HC095163 / HC / NHLBI NIH HHS / United States N01 HC095164 / HC / NHLBI NIH HHS / United States N01 HC095165 / HC / NHLBI NIH HHS / United States N01 HC095166 / HC / NHLBI NIH HHS / United States N01 HC095167 / HC / NHLBI NIH HHS / United States N01 HC095168 / HC / NHLBI NIH HHS / United States N01 HC095169 / HC / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-65226 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01-HC-95159 / HC / NHLBI NIH HHS / United States N01-HC-95160 / HC / NHLBI NIH HHS / United States N01-HC-95162 / HC / NHLBI NIH HHS / United States N01-HC-95163 / HC / NHLBI NIH HHS / United States N01-HC-95164 / HC / NHLBI NIH HHS / United States N01-HC-95165 / HC / NHLBI NIH HHS / United States N01-HC-95166 / HC / NHLBI NIH HHS / United States N01-HC-95167 / HC / NHLBI NIH HHS / United States N01-HC-95168 / HC / NHLBI NIH HHS / United States N01-HC-95169 / HC / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States R01 HL046380 / HL / NHLBI NIH HHS / United States R01 HL095603 / HL / NHLBI NIH HHS / United States R01 HL46380-01 / HL / NHLBI NIH HHS / United States R01-HL095603 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States |