A comparison of combinatorial partitioning and linear regression for the detection of epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms on plasma PAI-1 levels.
The detection and characterization of epistasis or non-additive gene-gene interactions remains a statistical challenge in genetic epidemiology. The recently developed combinatorial partitioning method (CPM) may overcome some of the limitations of linear regression for the exploratory analysis of non-additive epistatic effects. The goal of this study was to compare CPM with linear regression analysis for the exploratory analysis of non-additive interactive effects of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) and plasminogen activator inhibitor 1 (PAI-1) 4G/5G polymorphisms on plasma PAI-1 levels in a sample of 50 unrelated African Americans and 117 unrelated Caucasians. Using linear regression, we documented the additive effects of the ACE and PAI-1 genes on plasma PAI-1 levels in African American females (R(2) = 0.10), African American males (R(2) = 0.16), Caucasian females (R(2) = 0.11), and Caucasian males (R2 = 0.09). Using CPM, we found evidence for non-additive effects of the ACE and PAI-1 genes in both African American females (R(2) = 0.22) and African American males (R(2) = 0.24) but not in Caucasian females (R(2) = 0.10) or Caucasian males (R(2) = 0.11). The results of this exploratory data analysis support previous experimental, clinical, and epidemiological studies that have proposed as a working hypothesis that the ACE gene mediates interaction effects of the fibrinolytic and renin-angiotensin systems on plasma levels of PAI-1.
Program in Human Genetics, Department of Molecular Physiology and Biophysics, 519 Light Hall, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA. moore@phg.mc.vanderbilt.edu
J H
JH
Moore
J M
JM
Lamb
N J
NJ
Brown
D E
DE
Vaughan
D044383:Black People; D015992:Body Mass Index; D003627:Data Interpretation, Statistical; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D044465:White People; D001741:Black or African American
D017395:Plasminogen Activator Inhibitor 1; D007703:Peptidyl-Dipeptidase A