PCOS and Genetics [Part 1]

Discussing the world of genetics

Hello lovely people,

How was your week?

No matter how your week was, I hope your Sunday has allowed you a moment of peace and reflection ❤️.

A fascinating topic is coming today and in the following newsletters: GENETICS.

Slightly scary and powerful influence on our PCOS, but knowledge is power. At the PCOS Newsletter, we aim to understand our bodies in depth. There is nothing more deep about us than our genetic make-up. Let’s gooooo….

How did we form?

Our basic form is atoms. Atoms together create a molecule.

One of the most incredible gifts from our evolution is the ability for some molecules to self-replicate. Copying the initial molecule millions and millions of times. With the copying process, mistakes happen. As you’d copy a document millions of times, mistakes are bound to happen.

These mistakes have helped us evolve from an atom to what we are today. And if the environment keeps changing, “mistakes” will keep happening for this new organism to adjust to its new environment. It’s hard to think about us humans as just a bundle of millions and millions of molecules colliding together, but according to science, we are just that.

Depending on how religious you are, you might resonate with this theory of evolution to different degrees. Regardless of your beliefs, we must agree it’s freaking amazing how our body works and the complexity that is at play for us to survive and do the little silly things we do: drinking our coffee, walking or talking…

DNA

Over time, these self-replicating molecules developed defencing mechanisms to stay alive. A lot of them died out, but those who survived are those who adapted and created ways for them to be protected. Just consider our skin, muscles and bones as an example here. Our skin, bones and muscles are a strong protective layer for our organs. Our tissues are a strong protective layer for our cells. And our cells have a robust membrane that protects our main replicating machine: our DNA!

If you consider that, ultimately, we are the carriers of these main replicating molecules: DNA, you start understanding why humans behave the way they do. It’s all for the aim of “survival” to keep replicating. For survival, we need a lot of different things: oxygen, food, water, etc., and we will go to great lengths to ensure we have them, including killing other organisms such as animals or humans themselves (as it’s the case in war).

But why am I telling you all of this?

I am telling you all of this because we are going to touch on mutations and how the bodies of those with PCOS might act a bit differently than others. I want you to see this as ‘natural’. In specific environments, the way this self-replicating machine behaves will change. Understanding it can help us work with what we have and consider if changing the conditions of our environment (Eg. ⬇️ insulin levels) may change how the replicating machine works.

But to know how to do that, we must understand our genetic make-up.

Are you with me? I hope I haven’t lost you by now.

Guess what? I got the genetic makeup of my own body, and we will explore it together in the following newsletters.

What is this replicating machine?

Our DNA can be found inside our cells, in the nucleus. The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T).

Human DNA consists of about 3 billion of these bases, and more than 99% are identical in everyone.

As described above, DNA can replicate or make copies of itself. Each strand of DNA can serve as a pattern for duplication. This is critical when cells divide because each new cell needs an exact copy of the DNA in the old cell.

What does DNA do?

DNA contains the instructions for an organism to develop, survive and reproduce. These instructions are called genes. It is thought that our body has between between 20,000 and 25,000 genes. We get a copy of DNA from our mom and a copy from our dad.

Genes help us code for proteins. Proteins are the building blocks of how our body is formed and survives. Let’s take an example so we can put all of this into perspective:

DNA → Gene → Protein → Hormone with a role in the body → Survival

Our genes, specifically the thyroid's thyroglobulin gene (Tg), starts creating a protein: thyroglobulin. This is the basic unit of our thyroid hormone. The genes, taking instructions from our DNA, have just created one of the building blocks for us to survive. Together with iodine, this becomes your well-known T3 and T4 hormones that you measure on blood tests. These T3 and T4 will travel through the body and stimulate energy production, making you survive.

PCOS Genetics

As you are reading this, your DNA keeps replicating and creating proteins for you to survive. Sometimes, it makes mistakes, or the environment changes the way it copies itself. These mistakes are natural, and they might have happened in past generations, which got passed down to you. These are called genetic variations (mutations).

Occasionally, one or both parents pass on instructions that have a small error in them. This error is more commonly known as a single nucleotide polymorphism (SNP). We pronounce this as ‘snip’. Most SNPs have no effect on you or your life but some do.

SNPs can result in the resulting protein behaving differently. In many cases, this means the protein's function is not as efficient as we would like it to be. In other words, the protein does not carry out its role as expertly as we would like it to.

These are all the genes variations associated with PCOS:

However, no single gene mutation was identified as the common cause of PCOS.

Given how complex PCOS is, you can see that these genes are associated with different parts of our body.

We will dive into the most important ones in the following newsletter. This will be an exciting 3 weeks at The PCOS Newsletter. I promised you we would go deeper into our understanding of our own bodies in 2024, and this is what we are doing.

See you next Sunday,

Francesca

¹ Sources

1. BRCA gene mutations: Cancer risk and genetic testing. (2020, November 25). National Cancer Institute. https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

Combs, J. C., Hill, M. J., & Decherney, A. H. (2021). Polycystic ovarian syndrome genetics and epigenetics. Clinical Obstetrics and Gynecology, 64(1), 20–25. https://doi.org/10.1097/grf.0000000000000581

Dawkins, R. (2016). The Selfish Gene: 40Th Anniversary edition (4th ed.). Oxford University Press.

Day, F., Karaderi, T., Jones, M. R., Meun, C., He, C., Drong, A., Kraft, P., Lin, N., Huang, H., Broer, L., Magi, R., Saxena, R., Laisk, T., Urbanek, M., Hayes, M. G., Thorleifsson, G., Fernandez-Tajes, J., Mahajan, A., Mullin, B. H., … the 23andMe Research Team. (2018). Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genetics, 14(12), e1007813. https://doi.org/10.1371/journal.pgen.1007813

Deoxyribonucleic acid (DNA) fact sheet. (2019, March 9). Genome.gov; NHGRI. https://www.genome.gov/about-genomics/fact-sheets/Deoxyribonucleic-Acid-Fact-Sheet

Khan, M. J., Ullah, A., & Basit, S. (2019). Genetic basis of polycystic ovary syndrome (PCOS): Current perspectives. The Application of Clinical Genetics, 12, 249–260. https://doi.org/10.2147/tacg.s200341

Liu, A. L., Xie, H. J., Xie, H. Y., Liu, J., Yin, J., Hu, J. S., & Peng, C. Y. (2017). Association between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome: a systematic review and meta-analysis. BMC Medical Genetics, 18(1). https://doi.org/10.1186/s12881-017-0452-1

Makhdoomi, M. J., Shah, I. A., Rashid, R., Rashid, A., Singh, S., Shah, Z. A., & Ganie, M. A. (2023). Effect modification of LHCGR gene variant (rs2293275) on clinico-biochemical profile, and levels of luteinizing hormone in polycystic ovary syndrome patients. Biochemical Genetics, 61(4), 1418–1432. https://doi.org/10.1007/s10528-022-10327-z

Moraru, A., Cakan-Akdogan, G., Strassburger, K., Males, M., Mueller, S., Jabs, M., Muelleder, M., Frejno, M., Braeckman, B. P., Ralser, M., & Teleman, A. A. (2017). THADA regulates the organismal balance between energy storage and heat production. Developmental Cell, 41(1), 72-81.e6. https://doi.org/10.1016/j.devcel.2017.03.016

National Institutes of Health (US), & Biological Sciences Curriculum Study. (2007). Understanding human genetic variation. National Institutes of Health.

Prapas, N., Karkanaki, A., Prapas, I., Kalogiannidis, I., Katsikis, I., & Panidis, D. (2009). Genetics of polycystic ovary syndrome. Hippokratia, 13(4), 216.

Sinclair, D. A. (2021). Lifespan: Why we age - and why we don’t have to. Thorsons.

Singh, S., Kaur, M., Kaur, R., Beri, A., & Kaur, A. (2022). Association analysis of LHCGR variants and polycystic ovary syndrome in Punjab: a case–control approach. BMC Endocrine Disorders, 22(1). https://doi.org/10.1186/s12902-022-01251-9

Disclaimer: We are all unique in our ways, so this information is for educational purposes only. In my communications, I summarise research data and bring my experience. This shouldn’t be viewed as medical advice at any point. Please further consult your healthcare provider about your health needs.