In the post-genome era,different omics methods have been used to establish the relationship between clinical phenotypes and molecular characterizations.The combination of genomics,proteomics,and metabolomics has unraveled the etiology and pathophysiology of various diseases in a big-data fashion and the recent Genome-Wide Association Studies(GWAS)have provided a powerful systematic method to investigate the impact of common genomic variations on human cardiovascular pathophysiology and disease.But,these studies also revealed unmatched relationships between the genomic variability and the much narrower definition of various clinical phenotypes of cardiovascular diseases in individual patients.In the majority of GWAS a single targeted disease or a pre-defined and limited phenotype(trait)was studied and the accrual of such a large number of single gene variant-phenotype associations has led to the serendipitous identification of single loci associated with multiple diseases,or one gene being responsible or affecting more than one phenotypic characteristic(pleiotropy).Clearly,Western medicine is now facing the same challenges as traditional Chinese medicine(TCM)and newer approaches are needed for the redefinition of diseases using the underlying molecular causes and other factors in addition to traditional signs and symptoms.These are the same old questions for TCM for many years.A new method named″Phenome-Wide Association Study(PheWAS)″as an alternative approach that complements GWAS and utilizes phenomics and big-data technologies to analyze all genetic/proteomic variants and all available phenotypic information in the estimation of association between genome-phenome and detection of pleiotropy.Phenomics is a recently developed new transdiscipline that provides a suite of new technologies and platforms for the transition from focused phenotype-genotype study to a systematic phenome-genome approach,which can be used to redefine the clinical phenotypes of diseases.Accordingly,disease will be defined as a clinical phenome that is the sum total of a patient′s clinical characteristics or phenomic traits that signify the expression of the whole genome,proteome,and metabolome under specific environmental influence.With the fast advance and development of big-data technology and phenomics,we believe that the application of PheWAS in medicine opens important avenues to enhance systematically-integrated analysis of the genomic basis of human disease and responses to drug therapy and to reform our understanding and clinical treatment of diseases with a new concept of wholism.With well-defined clinical disease phenome,a new transdiscipline termed″pharmacophenomics″has been emerging.As a complement of pharmacogenomics,pharmacoproteomics,and pharmacometabolomics,pharmacophenomics offers a suite of new technologies and platforms for the transition from focused phenotype-genotype study to a systematic phenome-genome approach and refine drug research with systematically-defined drug response and therapeutic targets.Therefore,pharmacophenomics will provide a new paradigm for the study of drug response including effects and toxicities at the level of systems biology and will identify the corresponding therapeutic targets suitable for personalized medicine.
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