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• W1941255455 endingPage "e0136379" @default.
• W1941255455 startingPage "e0136379" @default.
• W1941255455 abstract "Plasminogen activator inhibitor 1 (PAI-1), a major modulator of the fibrinolytic system, is an important factor in cardiovascular disease (CVD) susceptibility and severity. PAI-1 is highly heritable, but the few genes associated with it explain only a small portion of its variation. Studies of PAI-1 typically employ linear regression to estimate the effects of genetic variants on PAI-1 levels, but PAI-1 is not normally distributed, even after transformation. Therefore, alternative statistical methods may provide greater power to identify important genetic variants. Additionally, most genetic studies of PAI-1 have been performed on populations of European descent, limiting the generalizability of their results. We analyzed >30,000 variants for association with PAI-1 in a Ghanaian population, using median regression, a non-parametric alternative to linear regression. Three variants associated with median PAI-1, the most significant of which was in the gene arylsulfatase B (ARSB) (p = 1.09 x 10−7). We also analyzed the upper quartile of PAI-1, the most clinically relevant part of the distribution, and found 19 SNPs significantly associated in this quartile. Of note an association was found in period circadian clock 3 (PER3). Our results reveal novel associations with median and elevated PAI-1 in an understudied population. The lack of overlap between the two analyses indicates that the genetic effects on PAI-1 are not uniform across its distribution. They also provide evidence of the generalizability of the circadian pathway’s effect on PAI-1, as a recent meta-analysis performed in Caucasian populations identified another circadian clock gene (ARNTL)." @default.
• W1941255455 created "2016-06-24" @default.
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• W1941255455 date "2015-08-31" @default.
• W1941255455 modified "2023-10-13" @default.
• W1941255455 title "Genetics of Plasminogen Activator Inhibitor-1 (PAI-1) in a Ghanaian Population" @default.
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• W1941255455 doi "https://doi.org/10.1371/journal.pone.0136379" @default.
• W1941255455 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4556460" @default.
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