Perspective
Letting the Genome out of the Bottle — Will We Get Our Wish?
N Engl J Med 2008; 358:105-107January 10, 2008
- Article
It may happen soon. A patient, perhaps one you have known for years, who is overweight and does not exercise regularly, shows up in your office with an analysis of his whole genome at multiple single-nucleotide polymorphisms (SNPs). His children, who were concerned about his health, spent $1,000 to give him the analysis as a holiday gift. The test report states that his genomic profile is consistent with an increased risk of both heart disease and diabetes, and because the company that performed the analysis stated that the test was “not a clinical service to be used as the basis for making medical decisions,” he is in the office for some “medical direction.” What should you do?
This year has seen a dizzying number of genomewide association studies demonstrating associations between novel gene variants or chromosomal loci and common diseases and phenotypes. These studies rely on microarrays that can assess 300,000 or more SNPs in each DNA sample; researchers use these microarrays to examine interpersonal differences in inherited genetic variability and to compare the prevalence of gene variants among patients who have a given disease with that among controls. Such studies have identified associations with many gene variants that were not previously suspected to be related to the phenotypes under consideration. The new technologies involved have been a boon to researchers who needed unbiased clues as to the causation of diseases that may be used to develop new therapeutic and preventive interventions. The test undergone by the patient described above is one of the products of this new knowledge.
As of November 2007, two companies have made available direct-to-consumer “personal genome services” (www.23andme.com) or “gene profiles” (www.decodeme.com) that rely on the same arrays of 500,000 to 1 million SNPs used in genomewide association studies. A third company (www.navigenics.com) has announced that it will offer similar services later this year. Essentially, a client sends a DNA sample to one of these firms, which analyzes the sample by means of SNP array; the data are stored in an online private account, the results are compared with allele–phenotype databases maintained and updated by the company, and the customer receives a readout of his or her levels of risk for specific conditions.
But such premature attempts at popularizing genetic testing seem to neglect key aspects of the established multifaceted evaluation of genetic tests for clinical applications. First, there is the question of a test's analytic validity, “its ability to accurately and reliably measure the genotype of interest.”1 Although appropriate monitoring and oversight of the analytic validity of genetic tests remain largely unaddressed,2 most researchers report that the analytic validity of these platforms is very high. It is likely that sample-handling errors are a greater threat to the validity of results than are genotypic misclassification errors. Yet even very small error rates per SNP, magnified across the genome, can result in hundreds of misclassified variants for any individual patient. Without transparent quality-control monitoring and proficiency testing, the real-world performance of these platforms is uncertain.
Second, one must consider clinical validity, or the ability of the test to detect or predict the associated disorder.1 Components of clinical validity include the test's sensitivity, specificity, and positive and negative predictive value. This is the area in which the data are in the greatest flux, and even the ardent proponents of genomic susceptibility testing would agree that for most diseases, we are still at the early stages of identifying the full list of susceptibility-associated variants. Most of the diseases listed by the direct-to-consumer testing companies (e.g., diabetes, various cancers, and heart disease) are so-called complex diseases thought to be caused by multiple gene variants, interactions among these variants, and interactions between variants and environmental factors. Thus, a full accounting of disease susceptibility awaits the identification of these multiple variants and their interactions in well-designed studies. What we have now is recognition of a limited number of variants associated with relative risks of diseases on the order of 1.5 or lower. Risk factors with this level of relative risk clearly do a poor job of distinguishing people who will develop these diseases from those who will not.3,4
Finally, there is the issue of the test's clinical utility, or the balance of its associated risks and benefits if it were to be introduced into clinical practice.1 Measures of utility address the question at the heart of the clinical application of a test: If a patient is found to be at risk for a disease, what can be done about it? This is the arena in which there are virtually no data available on the health impact of genomewide analysis. There are very few observational studies and almost no clinical trials that demonstrate the risks and benefits associated with screening for individual gene variants — let alone testing for many hundreds of thousands of variants. Thus, any claim to clinical utility currently rests on the assumption that interventions that have proven successful in the general population will behave the same way in a genetically at-risk population. Many of these interventions — such as smoking cessation, weight loss, increased physical activity, and control of blood pressure — are likely to be broadly beneficial in relation to many diseases, regardless of a person's genetic susceptibility to a specific disease.
It may be argued that knowledge of increased susceptibility to a disease, such as type 2 diabetes, for which protective lifestyle interventions exist, will motivate patients to follow relevant recommendations. Yet as intuitively appealing as this contention may be, evidence to support it, particularly in the case of low-penetrance alleles, is scanty. The flip side, of course, is that patients who test negative may be falsely reassured and thus less motivated to comply with preventive recommendations. In the absence of evidence of efficacy, this rationale for susceptibility testing should be regarded with skepticism.
So what advice should a physician offer patients? For the patient who appears with a genome map and printouts of risk estimates in hand, a general statement about the poor sensitivity and positive predictive value of such results is appropriate, but a detailed consumer report may be beyond most physicians' skill sets. For the patient asking whether these services provide information that is useful for disease avoidance, the prudent answer is “Not now — ask again in a few years.” More information is needed on the clinical utility of this information in the light of existing disease-specific opportunities for prevention or early detection and the potential value that genomic profiles can add to that of simpler tools, such as the family health history. Finally, given the risk of commercial exploitation, if patients are determined to proceed, perhaps because they are simply curious, are genetic hobbyists, or are “early adopters” of new technology, it would make sense to encourage them to enroll in formal scientific studies.
Now that the genome is out of the bottle, how will our wish for better health be granted? Just as the emergence of a commercial entity (Celera) with ambitions to sequence the human genome spurred public projects to accelerate their efforts, perhaps the emergence of commercial personalized genomic services will galvanize efforts to plan and conduct the necessary translational research5 for the rational integration of genomic information into medical training and practice. Until the genome can be put to useful work, the children of the man described above would have been better off spending their money on a gym membership or a personal trainer so that their father could follow a diet and exercise regimen that we know will decrease his risk of heart disease and diabetes.
The opinions expressed in this article do not necessarily reflect the views of the Department of Health and Human Services. An interview with Dr. Muin Khoury, director of the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, can be heard at www.nejm.org.
Source Information
Dr. Hunter is a professor in the Departments of Epidemiology and Nutrition at the Harvard School of Public Health, Boston, and a statistical consultant to the Journal. Dr. Khoury is the director of the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, Atlanta. Dr. Drazen is the editor-in-chief of the Journal.
- References
References
1
Haddow JE, Palomaki GE. ACCE: a model process for evaluating data on emerging genetic tests. In: Khoury MJ, Little J, Burke W, eds. Human genome epidemiology: a scientific foundation for using genetic information to improve health and prevent disease. New York: Oxford University Press, 2004:217-33.
2
Draft report of the Secretary's Advisory Committee on Genetics, Health, and Society. U.S. System of Oversight of Genetic Testing 11-5-2007. (Accessed December 12, 2007, at http://www4.od.nih.gov/oba/sacghs/reports.)
3
Ware JH . The limitations of risk factors as prognostic tools. N Engl J Med 2006;355:2615-2617
Full Text | Web of Science | Medline4
Wald NJ ,Hackshaw AK ,Frost CD . When can a risk factor be used as a worthwhile screening test? BMJ 1999;319:1562-1565
CrossRef | Web of Science | Medline5
Khoury MJ ,Gwinn M ,Yoon PW ,Dowling N ,Moore CA ,Bradley L . The continuum of translation research in genomic medicine: how can we accelerate the appropriate integration of human genome discoveries into health care and disease prevention? Genet Med 2007;9:665-674
CrossRef | Web of Science | Medline
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J. C. Carroll, B. J. Wilson, J. Allanson, J. Grimshaw, S. M. Blaine, W. S. Meschino, J. A. Permaul, I. D. Graham. (2011) GenetiKit: a randomized controlled trial to enhance delivery of genetics services by family physicians. Family Practice 28:6, 615-623
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CrossRef12
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CrossRef13
Yeyang Su, Heidi C. Howard, Pascal Borry. (2011) Users’ motivations to purchase direct-to-consumer genome-wide testing: an exploratory study of personal stories. Journal of Community Genetics 2:3, 135-146
CrossRef14
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CrossRef15
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CrossRef16
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CrossRef17
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CrossRef18
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CrossRef19
Kathleen A. Calzone, Jean Jenkins, Cynthia A. Prows, Agnes Masny. (2011) Establishing the Outcome Indicators for the Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics. Journal of Professional Nursing 27:3, 179-191
CrossRef20
Kelly E Ormond, Louanne Hudgins, Jennifer M Ladd, David M Magnus, Henry T Greely, Mildred K Cho. (2011) Medical and graduate students' attitudes toward personal genomics. Genetics in Medicine 13:5, 400-408
CrossRef21
P. Borry, L. Henneman, P. Lakeman, L. P. ten Kate, M. C. Cornel, H. C. Howard. (2011) Preconceptional genetic carrier testing and the commercial offer directly-to-consumers. Human Reproduction 26:5, 972-977
CrossRef22
Kathryn T Hock, Kurt D Christensen, Beverly M Yashar, J Scott Roberts, Sarah E Gollust, Wendy R Uhlmann. (2011) Direct-to-consumer genetic testing: An assessment of genetic counselors' knowledge and beliefs. Genetics in Medicine 13:4, 325-332
CrossRef23
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CrossRef24
Richard R Sharp. (2011) Downsizing genomic medicine: Approaching the ethical complexity of whole-genome sequencing by starting small. Genetics in Medicine 13:3, 191-194
CrossRef25
A. Surbone. (2011) Social and ethical implications of BRCA testing. Annals of Oncology 22:Supplement 1, i60-i66
CrossRef26
Benjamin Djulbegovic, Iztok Hozo, Sander Greenland. 2011. Uncertainty in Clinical Medicine. , 299-356.
CrossRef27
Cinnamon S. Bloss, Eric J. Topol, Nicholas J. Schork. (2011) Association of direct-to-consumer genome-wide disease risk estimates and self-reported disease. Genetic Epidemiologyn/a-n/a
CrossRef28
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CrossRef29
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CrossRef32
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CrossRef33
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CrossRef35
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CrossRef37
A. L. McGuire, B. J. Evans, T. Caulfield, W. Burke. (2010) Regulating Direct-to-Consumer Personal Genome Testing. Science 330:6001, 181-182
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CrossRef47
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Full Text48
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CrossRef49
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CrossRef50
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CrossRef51
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CrossRef52
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CrossRef53
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CrossRef54
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CrossRef55
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CrossRef56
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CrossRef57
Raffaele De Caterina. (2010) Opportunities and Challenges in Nutrigenetics/Nutrigenomics and Health. Journal of Nutrigenetics and Nutrigenomics 3:4-6, 137-143
CrossRef58
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CrossRef59
Dimitrios H Roukos. (2010) Novel clinico–genome network modeling for revolutionizing genotype–phenotype-based personalized cancer care. Expert Review of Molecular Diagnostics 10:1, 33-48
CrossRef60
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CrossRef61
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CrossRef62
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CrossRef63
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CrossRef64
R. M. Simon, S. Paik, D. F. Hayes. (2009) Use of Archived Specimens in Evaluation of Prognostic and Predictive Biomarkers. JNCI Journal of the National Cancer Institute 101:21, 1446-1452
CrossRef65
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CrossRef66
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CrossRef67
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CrossRef68
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CrossRef69
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CrossRef70
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CrossRef71
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CrossRef72
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CrossRef73
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CrossRef74
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CrossRef75
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CrossRef78
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Christopher F. C. Jordens, Ian H. Kerridge, Gabrielle N. Samuel. (2009) Direct-to-Consumer Personal Genome Testing: The Problem Is Not Ignorance–It Is Market Failure. The American Journal of Bioethics 9:6-7, 13-15
CrossRef83
Michelle L. McGowan, Marcie A. Lambrix. (2009) Are Social Networkers and Genome Testers One in the Same? The Limitations of Public Opinion Research for Guiding Clinical Practice. The American Journal of Bioethics 9:6-7, 21-23
CrossRef84
Cynthia Marietta, Amy L. McGuire. (2009) Currents in Contemporary Ethics. The Journal of Law, Medicine & Ethics 37:2, 369-374
CrossRef85
Oksana A Makeeva, Valentina V Markova, Valery P Puzyrev. (2009) Public interest and expectations concerning commercial genotyping and genetic risk assessment. Personalized Medicine 6:3, 329-341
CrossRef86
Kenneth M. Weiss. (2009) How the Persians were saved by lightning. Evolutionary Anthropology: Issues, News, and Reviews 18:3, 85-90
CrossRef87
Peter Kraft, Sholom Wacholder, Marilyn C. Cornelis, Frank B. Hu, Richard B. Hayes, Gilles Thomas, Robert Hoover, David J. Hunter, Stephen Chanock. (2009) Beyond odds ratios — communicating disease risk based on genetic profiles. Nature Reviews Genetics 10:4, 264-269
CrossRef88
Sayoko E Moroi, Duna A Raoof, David M Reed, Sebastian Zöllner, Zhaohui Qin, Julia E Richards. (2009) Progress toward personalized medicine for glaucoma. Expert Review of Ophthalmology 4:2, 145-161
CrossRef89
Dimitrios H Roukos. (2009) Genome-wide association studies: how predictable is a person’s cancer risk?. Expert Review of Anticancer Therapy 9:4, 389-392
CrossRef90
Susan Hiraki, Clara A. Chen, J. Scott Roberts, L. Adrienne Cupples, Robert C. Green. (2009) Perceptions of Familial Risk in those Seeking a Genetic Risk Assessment for Alzheimer’s Disease. Journal of Genetic Counseling 18:2, 130-136
CrossRef91
R. Rand Allingham, Yutao Liu, Douglas J. Rhee. (2009) The genetics of primary open-angle glaucoma: A review. Experimental Eye Research 88:4, 837-844
CrossRef92
Dimitrios H. Roukos. (2009) Genome-Wide Association Studies and Aggressive Surgery Toward Individualized Prevention, and Improved Local Control and Overall Survival for Gastric Cancer. Annals of Surgical Oncology 16:4, 795-798
CrossRef93
Iftikhar J Kullo, Keyue Ding. 2009. Molecular Genetics of Susceptibility to Coronary Heart Disease. .
CrossRef94
Kjetil Søreide, Bjørn S. Nedrebø, Jens-Christian Knapp, Tom B. Glomsaker, Jon Arne Søreide, Hartwig Kørner. (2009) Evolving molecular classification by genomic and proteomic biomarkers in colorectal cancer: Potential implications for the surgical oncologist. Surgical Oncology 18:1, 31-50
CrossRef95
Dimitrios H. Roukos, Dimosthenis Ziogas. (2009) Human Genetic and Structural Genomic Variation: Would Genome-Wide Association Studies Be the Solution for Cancer Complexity Like Alexander the Great for the “Gordian Knot”?. Annals of Surgical Oncology 16:3, 774-775
CrossRef96
Dimitrios H. Roukos. (2009) Personal Genomics and Genome-Wide Association Studies: Novel Discoveries but Limitations for Practical Personalized Medicine. Annals of Surgical Oncology 16:3, 772-773
CrossRef97
Antonella Surbone. (2009) Legislation on genetic testing and the practice of oncology. Critical Reviews in Oncology/Hematology 69:2, 95-97
CrossRef98
Eleftheria Zeggini, John PA Ioannidis. (2009) Meta-analysis in genome-wide association studies. Pharmacogenomics 10:2, 191-201
CrossRef99
Anne V. Buchanan, Samuel Sholtis, Joan Richtsmeier, Kenneth M. Weiss. (2009) What are genes “for” or where are traits “from”? What is the question?. BioEssays 31:2, 198-208
CrossRef100
Steven W.J. Lamberts, André G. Uitterlinden. (2009) Genetic Testing in Clinical Practice. Annual Review of Medicine 60:1, 431-442
CrossRef101
K.E. Ormond, A.L. Cirino, I.B. Helenowski, R.L. Chisholm, W.A. Wolf. (2009) Assessing the understanding of biobank participants. American Journal of Medical Genetics Part A 149A:2, 188-198
CrossRef102
Fintan R Steele. (2009) Personalized medicine: something old, something new. Personalized Medicine 6:1, 1-5
CrossRef103
Dimitrios H Roukos. (2009) Assessing both genetic variation (SNPs/CNVs) and gene–environment interactions may lead to personalized gastric cancer prevention. Expert Review of Molecular Diagnostics 9:1, 1-6
CrossRef104
Steven M Teutsch, Linda A Bradley, Glenn E Palomaki, James E Haddow, Margaret Piper, Ned Calonge, W David Dotson, Michael P Douglas, Alfred O Berg. (2009) The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genetics in Medicine 11:1, 3-14
CrossRef105
Coral E. Gartner, Jan J. Barendregt, Wayne D. Hall. (2009) Multiple genetic tests for susceptibility to smoking do not outperform simple family history. Addiction 104:1, 118-126
CrossRef106
Juli Murphy, Joan Scott, David Kaufman, Gail Geller, Lisa LeRoy, Kathy Hudson. (2008) Public Expectations for Return of Results from Large-Cohort Genetic Research. The American Journal of Bioethics 8:11, 36-43
CrossRef107
Tanya Agurs-Collins, Muin J. Khoury, Denise Simon-Morton, Deborah H. Olster, Jennifer R. Harris, John A. Milner. (2008) Public Health Genomics: Translating Obesity Genomics Research Into Population Health Benefits. Obesity 16, S85-S94
CrossRef108
Meigs, James B., Shrader, Peter, Sullivan, Lisa M., McAteer, Jarred B., Fox, Caroline S., Dupuis, Josée, Manning, Alisa K., Florez, Jose C., Wilson, Peter W.F., D'Agostino, Ralph B. Sr., Cupples, L. Adrienne, . (2008) Genotype Score in Addition to Common Risk Factors for Prediction of Type 2 Diabetes. New England Journal of Medicine 359:21, 2208-2219
Full Text109
Barbara Prainsack, Jenny Reardon, Richard Hindmarsh, Herbert Gottweis, Ursula Naue, Jeantine E. Lunshof. (2008) Personal genomes: Misdirected precaution. Nature 456:7218, 34-35
CrossRef110
Sharon A Savage. (2008) Cancer genetic association studies in the genome-wide age. Personalized Medicine 5:6, 589-597
CrossRef111
J. Kaye. (2008) The regulation of direct-to-consumer genetic tests. Human Molecular Genetics 17:R2, R180-R183
CrossRef112
James P Evans. (2008) Recreational genomics; what's in it for you?. Genetics in Medicine 10:10, 709-710
CrossRef113
Steven AR Murphy, Jeffrey S Freed. (2008) Healthcare’s ascension to patient-centered genomic care. Personalized Medicine 5:5, 505-509
CrossRef114
Barbara Prainsack. (2008) What are the stakes? Genetic nondiscrimination legislation and personal genomics. Personalized Medicine 5:5, 415-418
CrossRef115
Dimitrios H Roukos. (2008) Genetics and genome-wide association studies: surgery-guided algorithm and promise for future breast cancer personalized surgery. Expert Review of Molecular Diagnostics 8:5, 587-597
CrossRef116
Peter Kraft. (2008) Curses—Winnerʼs and Otherwise—in Genetic Epidemiology. Epidemiology 19:5, 649-651
CrossRef117
Jochen D. Muehlschlegel, Simon C. Body. (2008) Impact of genetic variation on perioperative bleeding. American Journal of Hematology 83:9, 732-737
CrossRef118
John P. A. Ioannidis. (2008) Sequential Discovery, Thinking Versus Dredging, and Shrink or Sink. Epidemiology 19:5, 657-658
CrossRef119
Audrey Chapman. (2008) DTC Marketing of Genetic Tests: The Perfect Storm. The American Journal of Bioethics 8:6, 10-12
CrossRef120
Michelle L. McGowan, Jennifer R. Fishman. (2008) Using Lessons Learned From BRCA Testing and Marketing: What Lies Ahead for Whole Genome Scanning Services. The American Journal of Bioethics 8:6, 18-20
CrossRef121
A.-L. Boulesteix, C. Porzelius, M. Daumer. (2008) Microarray-based classification and clinical predictors: on combined classifiers and additional predictive value. Bioinformatics 24:15, 1698-1706
CrossRef122
Colleen M McBride, Sharon Hensley Alford, Robert J Reid, Eric B Larson, Andreas D Baxevanis, Lawrence C Brody. (2008) Putting science over supposition in the arena of personalized genomics. Nature Genetics 40:8, 939-942
CrossRef123
(2008) Symposium Abstracts. Clinical Chemistry and Laboratory Medicine 46:S1, S5-S169
CrossRef124
Jason W. Chien. (2008) “Sunbreaks” for critical care in the modern era of genetic epidemiology*. Critical Care Medicine 36:8, 2453-2455
CrossRef125
Morris W Foster, Richard R Sharp. (2008) The contractual genome: how direct-to-consumer genomic services may help patients take ownership of their DNA. Personalized Medicine 5:4, 399-404
CrossRef126
Heidi C Howard, Pascal Borry. (2008) Direct-to-consumer genetic testing: more questions than benefits?. Personalized Medicine 5:4, 317-320
CrossRef127
(2008) In need of counseling?. Nature Biotechnology 26:7, 716-716
CrossRef128
Wylie Burke, Patricia Kuszler, Helene Starks, Suzanne Holland, Nancy Press. (2008) Translational Genomics: Seeking a Shared Vision of Benefit. The American Journal of Bioethics 8:3, 54-56
CrossRef129
Morris W. Foster, Richard R. Sharp. (2008) Out of sequence: how consumer genomics could displace clinical genetics. Nature Reviews Genetics 9:6, 419-419
CrossRef130
(2008) Letting the Genome Out of the Bottle. New England Journal of Medicine 358:20, 2184-2185
Full Text131
José Antonio Iribarren Loyarte. (2008) Aplicabilidad de los estudios farmacogenéticos en la práctica clínica. Enfermedades Infecciosas y Microbiología Clínica 26, 45-54
CrossRef132
Amy L McGuire. (2008) 1000 Genomes: on the road to personalized medicine. Personalized Medicine 5:3, 195-197
CrossRef133
Jason D. Christie. (2008) The interleukin-6 gene and critical illness: Is inflammatory gene variation the key to personalized medicine in the intensive care unit?*. Critical Care Medicine 36:5, 1647-1649
CrossRef134
Charles L. Sawyers. (2008) The cancer biomarker problem. Nature 452:7187, 548-552
CrossRef135
Dan Hurley. (2008) Direct-to-Consumer Genetic Tests for Alzheimer Disease and More Hit Market. Neurology Today 8:7, 22,23
CrossRef136
Erin E. Tracy. (2008) Are Doctors Prepared for Direct-to-Consumer Advertising of Genetic Tests?. Obstetrics & Gynecology 111:4, 991
CrossRef137
GertJan B van Ommen, Martina C Cornel. (2008) Recreational genomics? Dreams and fears on genetic susceptibility screening. European Journal of Human Genetics 16:4, 403-404
CrossRef138
John C. Linton. (2008) Times are Changing in Academic Health Centers, or Maybe Not: Our Next National Conference. Journal of Clinical Psychology in Medical Settings 15:1, 84-86
CrossRef139
(2008) Positively disruptive. Nature Genetics 40:2, 119-119
CrossRef140
Jeantine E. Lunshof, Ruth Chadwick, George M. Church. (2008) Hippocrates revisited? Old ideals and new realities. Genomic Medicine 2:1-2, 1-3
CrossRef
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