Abstract and Introduction
Significant technological improvements over the last decade have led to a vast expansion in the understanding of the genomic architecture of human disease. However, the use of genomic information, so-called genomic medicine, in routine clinical care, has been slow in comparison to the growth in genomic discovery. The uptake of genomic technology into clinical practice will depend on physicians' perspectives of its utility in patient care. We review recent literature addressing physician attitudes regarding the usefulness and limitations of genomic testing. We conclude by proposing research areas to better understand the role physicians will play in the uptake of genomic information into clinical medicine.
Over the last decade since the complete sequencing of the human genome, technological innovations have made it possible to identify human genetic variation more accurately and efficiently, accelerating our ability to perform large-scale genomic studies to identify new associations between DNA variants and human disease. This technological progress has resulted in the ability of an individual to examine his or her entire genome for disease-associated variation, as opposed to focusing only on a specific gene or genes. In this paper, we use 'genomic testing' to mean any genotyping performed across an individual's entire set of genes. One such technology is the SNP array, which examines an individual's genotype at hundreds of thousands or millions of loci known to carry genetic variation common in the population. This technology has enabled genome-wide association studies (GWAS) that have uncovered associations between such SNPs and a diverse spectrum of diseases.[1,2] SNP arrays are also the basis for commercial direct-to-consumer (DTC) genetic testing by companies like 23 and Me, Inc., which has for several years marketed a test for ancestry-informative genetic markers and, until recently, for common disease-associated variants.[3,4] A second type of genomic testing is array comparative genomic hybridization, which detects copy-number variation, deletions and duplications of segments of DNA. Such testing has been most widely applied to perinatal diagnosis of rare syndromes and molecular characterization of cancer.[5,6] The most complete examination of an individual's genome is now possible through a third type of genomic testing, next-generation sequencing, which can genotype the majority of the human genome's 3 billion DNA base pairs (whole-genome sequencing) or just its protein-coding regions (whole-exome sequencing). This approach identifies common variation but also, unlike SNP arrays, allows the discovery of novel, often rare, genetic variation. As much of the variation uncovered by sequencing is very rare, the associations between sequenced variants and disease are less well studied, making clinical inferences challenging at present. However, sequencing technologies have recently been employed to elucidate the genetic etiologies of rare syndromes, demonstrating proof of concept of their application to clinical medicine.[7,8] What the genomic testing technologies above have in common is the ability to expand genotyping beyond single genes to the entire human genome simultaneously in a single test.
Traditional genetic testing has had two broad, sometimes overlapping, clinical applications: diagnosis and risk prediction. In the former, identification of a lesion in a gene or gene product known to be associated with a given disease can confirm a suspected diagnosis. One example is the diagnosis of cystic fibrosis from the detection of one of the well-characterized mutations in the CFTR gene. An example of genetic testing for risk prediction is testing for stereotypical mutations in the blood clotting factors prothrombin and Factor V, which can aid in assessing one's risk for venous thromboembolism. Genomic testing might be similarly applied for diagnosis and risk prediction. Next-generation sequencing has aided in the diagnosis of syndromic diseases, identifying rare genetic variants not detected by conventional diagnostic testing.[7,8] SNP arrays can use genotype at multiple loci across the genome to inform one's genetic susceptibility to a common disease such as Type 2 diabetes.[9,10]
The reduction in the cost of genomic testing and the numerous new associations between genomic loci and human disease have brought anticipation that genomic testing will soon penetrate routine clinical care, both for common and rare conditions. Physicians now stand at the interface between genomic discovery and patient care. Their perception of the utility of genomic testing, then, will be an important determinant of whether it sees widespread uptake into clinical medicine. Here, we discuss a selection of recent studies that shed light on the question of whether physicians think genomic medicine is useful for patient care. In particular, we focus on studies that have assessed how generalists, including primary care physicians, view this new technology. While many of the questions addressed in this perspective have analogs in pediatrics, we limit our discussion to the care of adult patients, because the ethics of applying genomic medicine to the clinical care of children is beyond the scope of this paper. We conclude by suggesting research areas needed to further identify how physicians might shape the future clinical integration of genomic testing.
Personalized Medicine. 2014;11(4):425-433. © 2014 Future Medicine Ltd.