23Genome- wide association studies (GWAS) have identifying approximately several
loci for common diseases and traits. These associations provided new insights into
pathophysiology, suggesting previously unsuspected causal pathways for common
diseases that will be of use in identifying new therapeutic targets and developing
targeted interventions based on genetically defi ned risks. Although GWAS have
identifi ed numerous loci contributing to common diseases, these explain a small
fraction of the genetic component in disease. Likely explanations are relatively
rare variations that are missed by such studies and the presence of gene-gene
interactions.
Gene by environment (GxE) interactions is also important in many human dis-
eases. Given the diffi culty of assessing environmental factors in typical human
studies, the presence of GxE interactions would reduce ability to detect important
susceptibility loci. GxE interactions affecting gene expression may be a common
and important contribution to complex diseases. Genetic analysis of thousands of
transcript abundance traits in human primary endothelial cell lines in response to
proinfl ammatory oxidized phospholipids implicated in cardiovascular disease
revealed that approximately one-third of most regulated transcripts, showed evi-
dence of GxE interactions (Romanoski et al. 2010 ). The interactions resulted pri-
marily from effects of distal-, trans-acting loci, but a striking example of a local-GxE
interaction was also observed for FGD6. Some of the distal interactions were vali-
dated by siRNA knockdown experiments. These fi ndings add to the understanding
of the overall architecture of complex human traits and are consistent with the
possibility that GxE interactions are responsible, in part, for the failure of associa-
tion studies to more fully explain common disease variation.
Role of Genetics in Development of Personalized Medicines
Advances in genetics will also help in understanding drug action pathways, identi-
fi cations of new targets, target validation and in silico screening. Companies that
incorporate both genetics and genomics in the drug discovery process will be the
ones to discover the innovative drugs of the future.
Genetic Databases
Several genetic databases, governmental as well as private, are being developed and
bring together streams of data about individuals. The best known of these is the
Icelandic health sector database, managed by deCODE Genetic Inc in Iceland. Such
databases include molecular genetic data, clinical data, lifestyle data, and genea-
logical data. Searching for causal associations between genetic and health phenom-
ena is not new. Considerable data has been collected on the classic mendelian
disorders and is used for patient care and counseling. The Online Mendelian
Inheritance in Man ( http://www.ncbi.nlm.nih.gov/Omim ) has a catalogue of genes and
Role of Genetics in Future Approaches to Healthcare