Posted on 31/01/2019 by David Burgess
Home testing kits are all the rage – but do you really want to know the secrets of your genome?
‘Gene test for sale on NHS,’ blared the headlines last weekend, sparking some anxiety and confusion. The story is that Genomics England, a company owned by the Department of Health, has announced that it’s seeking people who are willing to pay to have their DNA sequenced. The fee has not yet been specified but it will probably be around £500, depending on how much the analysis is subsidised. Each volunteer will receive a personalised health report and will agree to share their anonymised genetic data with researchers in the hope of improving genetic prediction of diseases and creating the sort of healthcare that’s fit for the future.
The story has caused quite a fuss. What if Genomics England gives people inaccurate information? How do we ensure the data stays private? Won’t asking people to pay create a ‘two-tier’ health system? But critics should remember that 15 million people worldwide have voted with their credit cards to pay direct-to-consumer (DTC) companies like 23andMe to find out about their ancestry and their genetic medical risks. The NHS is sensibly taking the first steps to ensure that at some future point genome sequencing will be available to everyone.
DTC companies focus on identifying effects of single genes like APOE (apolipo-protein E). One form of this gene, called APOE-e4, leads to a 40 per cent risk of getting Alzheimer’s disease if you inherit one copy from your mother and one from your father. Although there are thousands of such single-gene effects, they are rare. APOE-e4 is much more common than most but still only about 1 per cent of the population has this 40 per cent risk. Many people choose not to find out about their APOE genotype, including James Watson, who won the Nobel prize for discovering the structure of DNA. The reason, they would say, is that at present there is nothing you can do about the risk for Alzheimer’s disease other than the all-purpose dictum of eating more healthily, drinking less alcohol and getting more exercise; and perhaps the more specific advice of avoiding head injuries — boxing is definitely out. Others, myself included, would say that there are things you could do even now if you knew you had a 40 per cent risk of getting Alzheimer’s disease. For example, you could plan for it socially and economically, and you might want an extra dollop of carpe diem.
Although rare single-gene effects are devastating for those people affected, the vast bulk of medical burden in society comes from common disorders like cardio-vascular disease, obesity, alcoholism, schizophrenia and depression. These disorders are substantially genetic in origin — about half of the risk can be attributed to genes. However, the genetic risk is not due to just one or a hundred or even a thousand DNA differences. For common disorders, genetic risk is caused by tens of thousands of DNA differences. Even in the case of Alzheimer’s disease, most of the genetic risk is due to thousands of tiny DNA differences — APOE-e4 is just a bit player in the population as a whole.
The most important advance in the DNA revolution in the past few years is that we can sum these minuscule DNA effects in a composite score, called a polygenic (‘many gene’) score. Polygenic scores have become able to significantly predict common dis-orders from DNA alone. Importantly, these predictions can be made from birth just as well as later in life, because inherited DNA differences do not change from the moment of conception.
Although these first polygenic scores explain only about 3 to 5 per cent of the risk, they are already among the best predictors we have for some common diseases such as Alzheimer’s, obesity, heart disease, diabetes and inflammatory bowel disease. For example, recent research has shown that the current polygenic score for coronary artery disease can identify 8 per cent of the UK population who have a threefold increased risk for having a heart attack. For early onset heart attacks, a high polygenic score is ten times more predictive than the best predictor now in use, which is elevated cholesterol of the bad kind (low-density lipoprotein). It should be emphasised that these are early days in research on polygenic scores. Bigger and better studies are ongoing which will produce more powerful polygenic scores.
Many people seem concerned about the ethics of genomic testing, but isn’t it unethical as well as uneconomical not to let people know about their increased risk for heart attacks, especially when so much can be done to prevent them? Quite low-tech lifestyle changes such as losing weight and having blood pressure checks can save lives; preventing a single severe heart attack could save the NHS hundreds of thousands of pounds. Validated polygenic scores exist right now to predict the risk of many other preventable diseases. Polygenic scores are the perfect early warning system.
DNA needs to be genotyped only once and then the same genotyping results can be used to create hundreds of polygenic scores for a wide range of disorders. It’s not a question of whether we do it but rather when we do it. When universal genotyping happens, it will be a boon to research because, as the Health Secretary Matt Hancock says, ‘there are huge benefits to sequencing as many genomes as we can’ in order to create more powerful polygenic scores.
Genotyping in general and polygenic scores in particular could save the NHS financially by greatly increasing its ability to predict and therefore prevent problems. I don’t see how private insurance-based medical systems like those in the US can survive the DNA revolution. The bottom line for private insurance-based systems is money, not a healthy population. For example, from a strictly financial perspective, it makes sense for an insurance company to avoid insuring you if you are at genetic risk for some costly disease. If you can’t pay for your increased risk, you are out of luck.
In contrast, in a universal health-care system like the NHS, people are not denied treatment because they are unable to pay for it. Genetic risks and costs are shared across the population. The National Institute for Health and Care Excellence (Nice), which is independent of government, can make the difficult decisions that need to be made to balance costs and benefits of intervention and treatment in the population as a whole. The NHS could offer plans for intervention and monitoring to prevent genetic risks from becoming full-blown disorders, and they could also offer counselling as needed; if you are, for example, in that unlucky 1 per cent of the population that has a 40 per cent risk of having Alzheimer’s disease.
This is a great opportunity for Britain and for the NHS. In private insurance-based medical systems, hospitals get paid for treating illness, not for preventing it. In contrast, universal health-care systems like the NHS should be highly motivated to promote health and prevent illness. The availability of low-tech interventions to prevent problems, as in the case of heart attacks, pushes the cost-benefit ratio off the scale and will make it impossible to ignore the potential of polygenic scores for the NHS. Universal health care is not some kind of throwback to 1940s idealism. It is the only sensible way to provide health care in light of the DNA revolution.
Let the sequencing begin
Direct-to-consumer (DTC) companies read your DNA on what is called an ‘SNP chip’. This is an array the size of a postage stamp that determines hundreds of thousands of inherited DNA differences (single-nucleotide polymorphisms, SNPs) throughout the genome. Actual costs for genotyping one individual on an SNP chip is about £30. Until now, the DNA revolution has been powered by data from SNP chips.
In contrast, the NHS is offering to genotype nearly all (95 per cent+) of the six billion rungs in the spiral staircase of DNA, called whole-genome sequencing (WGS). That’s the DNA we inherit in the single cell with which we begin life, and it’s the same DNA in all the trillions of cells in our body. WGS is the end of the story in terms of our DNA inheritance.
When the human genome was first sequenced 15 years ago, it cost more than £1 billion. Technological advances have now brought the cost for WGS down to under £1,000, which is still at least ten times more expensive than an SNP chip. Some DTC companies are beginning to offer WGS with price tags beginning at about £1,500, although much of the cost depends on how analysis and interpretation is on offer. So if WGS on the NHS cost £500, this would be several times cheaper than the cheapest offer from a DTC company. Another huge difference is that, unlike the wild west of DTC companies, the NHS remains one of the most trusted institutions in the UK.
Given how cost-effective WGS will be for the NHS, it actually seems odd for the NHS to charge anything at all for this gene test, especially when the NHS has always been free at the point of delivery. Matt Hancock says that ‘healthy people should not have this service free on the NHS’, but why not? The point of WGS is to predict potential problems in apparently healthy people in order to prevent problems from occurring. Nonetheless, I’m sanguine about charging people at first: it’s a good idea to start with volunteers to avoid a possible privacy backlash, and paying customers are the ultimate volunteers.
In the end, I believe that universal availability of WGS free at the point of delivery is inevitable.
Robert Plomin is the author of Blueprint: How DNA Makes Us Who We Are and Professor of Behavioural Genetics at King’s College London.