It may not be long before it is feasible to get a whole-genome sequence on every newborn child in Australia. Surely this will represent a major advance in disease prevention? Surprisingly this is not so and a very recent study published in Science and Translational Medicine explains why.
The researchers from Johns Hopkins University in the US studied the data on the prevalence of 24 common diseases in thousands of identical twins collected by researchers in Norway, Finland, Sweden, Denmark and the US. Because identical twins share virtually identical genomes the frequency with which both are affected by the same disease gives a measure of the effects of genes in causing the disease.
The analysis showed that even in the best circumstances when we know all the genetic variations that affect disease risk (and we are a long way from that at present), for 23 of the 24 diseases, the majority of individuals will receive negative test results. These negative test results will not be very helpful as the risk of developing 19 of the 24 diseases in those who test negative will still be, at minimum, 50 - 80% of that in the general population. Kenneth Kinzler, Ph.D., co-director of the Ludwig Center at Johns Hopkins and professor of oncology, provides an example of what their analysis showed: "As many as two percent of women undergoing whole genome sequencing could receive a positive test result for ovarian cancer, alerting them that they have at least a one-in-ten chance of developing that cancer over their lifetime. The other 98 percent of women who receive a negative test for ovarian cancer will not be guaranteed a lifetime free of ovarian cancer because their risk of developing it is very similar to that of the general population.”
The researchers report that on the positive side, in the best-case scenario more than 90% of tested individuals might be alerted to a clinically significant predisposition to at least one disease. This might allow them to make appropriate lifestyle modifications to reduce the risk of developing that disease. However the Johns Hopkins research casts doubt on whether whole genome sequencing can reliably predict the majority of future medical problems that will be encountered by most people who take such tests.
"We believe that genomic tests will not be substitutes for current disease prevention strategies," says Bert Vogelstein, M.D., Clayton Professor of Oncology at the Johns Hopkins Kimmel Cancer Center, co-director of the Ludwig Center for Cancer Genetics, and investigator of the Howard Hughes Medical Institute. "Prudent screening, early diagnosis and prevention strategies, such as not smoking and removing early cancers, will be the keys to cutting disease death rates."
The diseases studied were:
Prostate Cancer Male
Type 1 Diabetes
Type 2 Diabetes
Gastro Oesophageal Reflux Disorder
Irritable Bowel Syndrome
Coronary heart disease
General Dystocia Female
Pelvic Organ Prolapse Female
Stress Urinary Incontinence Female
1. The Predictive Capacity of Personal Genome Sequencing DOI: 10.1126/scitranslmed.3003380 Sci Transl Med , (2012); Nicholas J. Roberts et al.
2. Science Daily
3. The New York Times
4. The Atlantic