title: Networks in Coronary Heart Disease Genetics As a Step towards Systems Epidemiology.
abstract: We present the use of innovative machine learning techniques in the understanding of Coronary Heart Disease (CHD) through intermediate traits, as an example of the use of this class of methods as a first step towards a systems epidemiology approach of complex diseases genetics. Using a sample of 252 middle-aged men, of which 102 had a CHD event in 10 years follow-up, we applied machine learning algorithms for the selection of CHD intermediate phenotypes, established markers, risk factors, and their previously associated genetic polymorphisms, and constructed a map of relationships between the selected variables. Of the 52 variables considered, 42 were retained after selection of the most informative variables for CHD. The constructed map suggests that most selected variables were related to CHD in a context dependent manner while only a small number of variables were related to a specific outcome. We also observed that loss of complexity in the network was linked to a future CHD event. We propose that novel, non-linear, and integrative epidemiological approaches are required to combine all available information, in order to truly translate the new advances in medical sciences to gains in preventive measures and patients care.
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, United Kingdom; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.affiliation: Medical Department-Bracco Pharmaceuticals, San Donato Milanese, Italy; current affiliation: Villa Santa Maria Institute, Tavernerio, Italy; Semeion Research Center of Sciences of Communication, Rome, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Grossi
authors.affiliation: Semeion Research Center of Sciences of Communication, Rome, Italy; Dept. of Mathematical and Statistical Sciences, University of Colorado at Denver, Denver, CO, United States of America.
authors.forename: Massimo
authors.initials: M
authors.lastname: Buscema
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000465:Algorithms; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged