Earlier this week was Rare Disease Day. Patient groups, patients, clinicians, research institutes and healthcare providers all use this day to talk about the importance of rare diseases in clinical practice and research. The main message is clear: Even though rare diseases individually only affect a small number of people, there are many rare diseases, so a lot of people are affected by them overall.
A large proportion of rare disease is thought be ‘genetic’. It is not always clear how ‘genetic’ is being defined, but typically it is being used to describe diseases that are caused by a mutation in a gene.
The frequently given answer to the question ‘What proportion of rare diseases is genetic?’ is ‘80%’. But where does this statistic come from?
What is a rare disease?
To understand how many rare diseases are genetic, let’s first look at what a rare disease actually is. The definitions used in different regions of the world are not exactly the same.
There is no global consensus on the definition of a rare disease. And of course some diseases will be rare in some parts of the world but not rare, or even common, in other parts of the world, adding further complexity.
How many rare diseases are there?
Overall, the number of rare diseases recognized under either system totals around 7000, or between 6000 and 8000. That’s not a very specific number. Global Genes has a list of rare diseases, but even they give an overall number of “approximately 7000” and caution against reproducing the list elsewhere because it changes often.
The National Organization for Rare Disorders (NORD) has a list on their own site with information about approximately 1200 rare diseases, and acknowledges that there are many more.
How many rare diseases are genetic?
Many of the various lists seem to be closer to lists of rare genetic diseases, rather than of rare diseases per se. Some rare diseases that are not genetic are included. For example, malaria is on the list, because it’s rare in Europe and North America. But there appears to be under-representation of the many non-genetic rare diseases. Even taking this into account finding evidence that 80% of rare diseases are genetic is very hard.
So I decided to see if I could track down the origin of the “80% of rare diseases are genetic” statement.
To illustrate the extent of the problem, the Wikipedia page for rare diseases currently mentions the “80% are genetic” statistic twice. Once with a “citation needed” warning, and once with a link to a webpage that is no longer available.
The 80% statistic is usually mentioned as an unquestionable fact, without source. When there is a source cited, it is sometimes the patient organisation EURORDIS. More specifically, I found some citations of a brochure published by EURORDIS in 2005. Indeed, this brochure mentions the 80% statistic – but it does not say where it comes from. It’s just another line in a fact sheet, much like the ones shared by everyone else.
At least fifteen years old
I used Google, Google Scholar, and the Internet Archive to try to find the first time the statistic was given. Some mentions cite the book, The NORD Guide to Rare Disorders, published in December 2002. But I also found it in a company’s press release from April 2002, again mentioned without any source attribution, and presented as an unequivocal fact.
This means that the notion that 80% of rare diseases are genetic has been in use for at least fifteen years. This is an incredibly long time in genetics! In April 2002 it still wasn’t even clear how many genes there are. The official sequence of the human genome hadn’t been published yet, and the draft genome sequence was only a year old.
That’s how old the 80% statistic is!
Why is the statistic used?
There is a joke that says that 73% of all statistics are made up on the spot. (Or 79%, or 83% – there are many different versions circulating online, and that’s part of the joke!). Was that what happened here, or did it originate from an estimated guess based on the number of rare diseases and the number of genetic diseases that were known at the time?
And why do people keep using it? Is it because it has been used so often people assume it must be true? Or perhaps because people find percentages reassuring and convincing? Or because it is helpful in emphasising the importance of genetics in rare disease?
The proportion of rare diseases that are genetic is not known
Our investigations lead us to believe that the statement “80% of rare diseases are genetic” should probably be considered folklore rather than fact. If anyone can provide evidence otherwise, or can provide the provenance of the statement please contact us. We would be delighted to find out.
Currently, it seems that it is not known what proportion of rare diseases are genetic. Moreover, it is not easily knowable, because the definition of rare disease is unclear and the cataloguing of rare diseases is not comprehensive.
Nevertheless, it is clear that many genetic diseases are rare and many rare diseases are genetic.
This seems to be justification enough for the huge, impressive, important local and global initiatives celebrated on Rare Disease Day.