PCOS and genetic research

Image of test tubes in a tray with someone dropping liquid into them using a pipette

Guest Blog by Professor Stephen Franks

One of the most frequently asked questions about PCOS is “what causes it?” to which the experts can only answer “we still do not know for sure”. But what has become clear in the last two decades is that genetics play a big part in the development of the syndrome. We know that PCOS tends to run in families and, about 15 years ago, an important Dutch study of twins found that PCOS was twice as common between identical than between non-identical twins. That is very strong evidence for genetics playing a major part. There have been a lot of studies looking at abnormalities in possible “candidate” genes. These are genes that are known to regulate specific biochemical “pathways” that have been shown to be abnormal in PCOS, for example, genes that control the production of androgens and the actions of insulin. But these studies have not been able to provide any real insight into the genetic basis of the syndrome and that has led towards the use of genome-wide association studies (GWAS) to try to identify genes that may be involved in causing PCOS.

The principle of GWAS studies is to make no assumptions about what genes contribute the cause of PCOS but rather to use “markers” to search the twenty thousand genes across all 23 pairs of human chromosomes to find out which ones are different between women with PCOS and a suitable control population. As you might imagine, this process requires a lot of modern technology and very sophisticated statistical analysis to identify genes that have small variations in structure between PCOS and control women. Most importantly, such studies require a very large number of participants in order to detect small but significant differences between genes in women with and without PCOS. So that has led to the formation of an international consortium of research groups from all over the world (including our own group in the UK) that have collaborated to provide some important new information.

As a result of this collaboration, there has been a recently published study that involved over 10,000 women with PCOS (and more than 100,000 controls)**. In this study, significant variations were found in 19 genes, most of which were unexpected and provide important new information about PCOS. So that is exciting in itself but the study also gave us important information about whether the same genes were involved irrespective of the criteria used for diagnosis of PCOS. It turns out that whether you have both menstrual cycle disturbances and unwanted body hair or whether just one or the other, the genetic background is the same. In other words, PCOS is one syndrome that has a variety of symptoms and biochemical features, rather than a collection of different disorders.

**If you are interested and would like details of the science involved, this publication can be found using this reference: Day et al, PloS Genetics 2018 Dec 19;14(12):e1007813.