A genetic association study of activated partial thromboplastin time in European Americans and African Americans: the ARIC Study.

TitleA genetic association study of activated partial thromboplastin time in European Americans and African Americans: the ARIC Study.
Publication TypeJournal Article
Year of Publication2015
AuthorsWeng, L-C, Cushman, M, Pankow, JS, Basu, S, Boerwinkle, E, Folsom, AR, Tang, W
JournalHum Mol Genet
Date Published2015 Apr 15
KeywordsAged, Atherosclerosis, Black or African American, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Kininogens, Male, Middle Aged, Neural Cell Adhesion Molecule L1, Partial Thromboplastin Time, Polymorphism, Single Nucleotide, Prospective Studies, Proteins, White People

Reduced activated partial thromboplastin time (aPTT) is a risk marker for incident and recurrent venous thromboembolism (VTE). Genetic factors influencing aPTT are not well understood, especially in populations of non-European ancestry. The present study aimed to identify aPTT-related gene variants in both European Americans (EAs) and African Americans (AAs). We conducted a genetic association study for aPTT in 9719 EAs and 2799 AAs from the Atherosclerosis Risk in Communities (ARIC) study. Using the Candidate Gene Association Resource (CARe) consortium candidate gene array, the analyses were based on ∼50 000 SNPs in ∼2000 candidate genes. In EAs, the analyses identified a new independent association for aPTT in F5 (rs2239852, P-value = 1.9 × 10(-8)), which clusters with a coding variant rs6030 (P-value = 7.8 × 10(-7)). The remaining significant signals were located on F5, HRG, KNG1, F11, F12 and ABO and have been previously reported in EA populations. In AAs, significant signals were identified in KNG1, HRG, F12, ABO and VWF, with the leading variants in KNG1, HRG and F12 being the same as in the EAs; the significant variant in VWF (rs2229446, P-value = 1.2 × 10(-6)) was specific to the AA sample (minor allele frequency = 19% in AAs and 0.2% in EAs) and has not been previously reported. This is the first study to report aPTT-related genetic variants in AAs. Our findings in AAs demonstrate transferability of previously reported associations with KNG1, HRG and F12 in EAs. We also identified new associations at F5 in EAs and VWF in AAs that have not been previously reported for aPTT.

Alternate JournalHum Mol Genet
PubMed ID25552651
PubMed Central IDPMC4375421
Grant ListR01-HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
R01 HL095603 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01-HL095603 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States

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