SOS: Save our Science - Inside Endometriosis

I wrote this after reading the BBC article about the same paper. The work was very poorly explained, and the findings were completely mistranslated. However, this time the original paper was pretty good, although filled with statistics (Bleh!)

All women hate periods, but a small percentage have it much worse than others. They suffer from endometriosis; severe pains and poor fertility throughout their reproductive life. The illness is often passed down through families, so must be partially dependent on genes. A new study has identified where some of these genes may occur.



First, a short comment on the BBC article, then I’ll give an accurate report.

This article actually did a very good job of keeping the claims realistic. It points out several times that lots more work needs to be done before this discovery can be put to good use, and reinforces this with similar quotes from the people involved. However, it blatantly name drops (Oxford & Harvard) to raise the profile of the work and the science is poorly conveyed.

The BBC report states that chromosomes 1 and 7 are responsible for the disease. You have about 10000 genes which determine who you are, there are stored as DNA code. The DNA code is broken into 23 separate pieces, these are chromosomes. You have 2 copies of each chromosome in every one of your cells, one from each parent. They are numbered according to size 1 to 22, largest to smallest, the 23rd pair are the sex chromosomes X and Y, determining if you are male or female. Chromosome 1, in particular, is very large and contains lots of different genes for doing different things. To say that it is involved in endometriosis is like saying the Internet is involved in spreading news; it may do that, but it also does a lot of other things. My favourite part said “Chromosome 1 is close to a gene which is important for hormone metabolism…” this line simultaneously manages to quote the paper almost perfectly, whilst completely destroying the meaning. A chromosome is a string of genes, it cannot be considered as being close to one gene. What they meant was, the part of chromosome 1 which is different from normal in people with endometriosis is relatively close to a gene (called WNT4) which is a key signal in development of female reproductive organs.

A big point is made of the need for surgery in identifying endometriosis. Whilst this is true, current methods involve laparoscopy (which is not as scary as the article makes it sound), also called keyhole surgery, which is considerably less dangerous and invasive than previous methods, although it does still require general anaesthetic.

The actual story

DNA stores information as an ordered sequence of four chemicals, these are typically referred to as A, C, G and T. There are 3 billion of these chemicals/letters in your genome. It is known that only some of these change very often between two different humans. The ones that change are called SNPs (or “snips”). So an SNP will have different forms, it can either be an A, C, G or T. One of these forms may cause an illness. In this study researchers looked for SNPs that have a particular form in people with endometriosis, and that do not take that form in unaffected people. By averaging over large groups of people (around 5500 endometriosis patients and around 10000 non-sufferers), it is possible to see patterns. An SNP with a specific form in people with a specific illness is usually close to a gene that affects that illness.

This kind of analysis is never clear cut, any identified changes are usually only in a few sufferers and also occur in plenty of non-sufferers. This is because many genes usually contribute to the effects of an illness, and environmental factors may also be important. After a lot of complex mathematical analysis, they were able to show that, in less than one percent of sufferers, part of chromosome 7 has one form that is not often seen in non-sufferers. Thus they were able to show that in a few cases this SNP contributes the endometriosis, the nearest genes (NEF2L3, HOXA10 and HOXA11) to this region are known to be active in the formation of female reproductive organs. This serves to support the finding that this change may lead to endometriosis.

This work in itself did not find anything significant (a statistical measure of importance and likely accuracy of data) on chromosome 1, but when combined with Japanese data from a previous paper (with many fewer samples), was able to support that an SNP on chromosome 1, close to WNT4, also favoured a particular form in some sufferers over non-sufferers. This highlights another interesting point, as different SNPs change more often in different races of humanity. The Japanese study identified an SNP involved in endometriosis in Japan but that never changes in Europeans (and also Australians and Americans which mostly descended from Europeans). One other interesting finding is that individuals with the most severe forms of endometriosis usually have the greatest number of changes favouring endometriosis, as may be logically expected.

Overall the study contributes a few more genetic markers which may indicate endometriosis, but many more remain to be identified before a reliable gene test can be developed to conclusively diagnose the illness. For now, laparoscopy is the only way.