TY - JOUR
T1 - Genetic Effects on the Correlation Structure of CVD Risk Factors
T2 - Exome-Wide Data From a Ghanaian Population
AU - Kodaman, Nuri
AU - Sobota, Rafal S.
AU - Asselbergs, Folkert W.
AU - Oetjens, Matthew T.
AU - Moore, Jason H.
AU - Brown, Nancy J.
AU - Aldrich, Melinda C.
AU - Williams, Scott M.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Plasma concentration of plasminogen activator inhibitor-1 (PAI-1) is highly correlated with several cardiovascular disease (CVD) risk factors. It also plays a direct role in CVD, including myocardial infarction and stroke, by impeding the dissolution of thrombi in the blood. Insofar as PAI-1 links CVD's risk factors to its endpoints, genetic variants modulating the relationship between PAI-1 and risk factors may be of particular clinical and biological interest. The high heritability of PAI-1, which has not been explained by genetic association studies, may also, in large part, be due to this relationship with CVD risk factors. Using exome-wide data from 1,032 Ghanaian study participants, we tested for heterogeneity of correlation by genotype between PAI-1 and 4 CVD risk factors (body mass index, triglycerides, mean arterial pressure, and fasting glucose) under the hypothesis that loci involved in the relationship between PAI-1 and other risk factors will also modify their correlational structure. We found more significant heterogeneities of correlation by genotype than we found marginal effects, with no evidence of type I inflation. The most significant result among all univariate and multivariate tests performed in this study was the heterogeneity of correlation between PAI-1 and mean arterial pressure at rs10738554, near SLC24A2, a gene previously associated with high blood pressure in African Americans.
AB - Plasma concentration of plasminogen activator inhibitor-1 (PAI-1) is highly correlated with several cardiovascular disease (CVD) risk factors. It also plays a direct role in CVD, including myocardial infarction and stroke, by impeding the dissolution of thrombi in the blood. Insofar as PAI-1 links CVD's risk factors to its endpoints, genetic variants modulating the relationship between PAI-1 and risk factors may be of particular clinical and biological interest. The high heritability of PAI-1, which has not been explained by genetic association studies, may also, in large part, be due to this relationship with CVD risk factors. Using exome-wide data from 1,032 Ghanaian study participants, we tested for heterogeneity of correlation by genotype between PAI-1 and 4 CVD risk factors (body mass index, triglycerides, mean arterial pressure, and fasting glucose) under the hypothesis that loci involved in the relationship between PAI-1 and other risk factors will also modify their correlational structure. We found more significant heterogeneities of correlation by genotype than we found marginal effects, with no evidence of type I inflation. The most significant result among all univariate and multivariate tests performed in this study was the heterogeneity of correlation between PAI-1 and mean arterial pressure at rs10738554, near SLC24A2, a gene previously associated with high blood pressure in African Americans.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85017372283&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/28408189
U2 - https://doi.org/10.1016/j.gheart.2017.01.013
DO - https://doi.org/10.1016/j.gheart.2017.01.013
M3 - Review article
C2 - 28408189
SN - 2211-8160
VL - 12
SP - 133
EP - 140
JO - Global Heart
JF - Global Heart
IS - 2
ER -