PCOS often runs in families with a 5x increased risk of having the condition if your biological mother has it.[1]  You have a 60-70% chance of having PCOS if your biological mother has PCOS[2] and a 50% chance if your biological sister has PCOS.[3]  In this article we explore the link between PCOS and genetics.

The underlying cause of PCOS is a result of a complex interaction of genetic, epigenetic and environmental factors.[4]

Genetic factors relate to how individual or groups of genes are implicated in health and disease.[5]  The genetic link underlying PCOS is far more complex than a single inherited gene and genetic factors explain less than 10% of PCOS heritability.[6] 

Epigenetic factors relate to how genes are expressed or function, in response to the environmental factors within the womb or later in life.[7]

Environmental factors include lifestyle, diet, stress / trauma and exposure to endocrine-disruptors,[8] natural or man-made chemicals that may mimic, block or interfere with the body’s hormones.[9]

There are more than 240 genetic variations and 29 genetic loci (specific regions of DNA) associated with PCOS.[10],[11],[12],[13]  Certain groups of genes have been identified that influence some of the primary characteristics associated with PCOS, including:

• Androgen excess: DENND1A, CYP17A1 and SHBG contribute to elevated androgens and therefore lead to changes in appearance such as acne and hirsutism; [14],[15]

• Hormonal regulation: FSHB, FSHR and LHCGR affect signaling of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and therefore influence ovulation and menstrual cycles;[16],[17]

• Ovarian function: AMH, ERBB4 and GATA4 regulate follicle maturation and ovarian reserve and therefore influence ovulation and fertility; [18],[19]

• Ovarian aging: CHEK2 and RAD50 are believed to play a role in reproductive aging and egg quality and therefore influence fertility;[20]

• Metabolic dysfunction: THADA, FTO, INSR and HMGA2 are associated with insulin resistance, obesity and Type 2 diabetes;[21],[22] and

• Inflammation: TOX3, YAP1 and MAPRE1 are linked to chronic inflammation.[23]

Reviewed by Malav Trivedi PhD. FRSB, expert on epigenetics.

Sources

[1] https://www.nature.com/articles/s41591-019-0666-1

[2] https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00004-8

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883751/

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883751/

[5] https://www.cdc.gov/genomics/about/basics.htm

[6] https://academic.oup.com/jcem/article/98/12/4565/2833703

[7] https://www.cdc.gov/genomics/disease/epigenetics.htm

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864804/

[9] https://www.niehs.nih.gov/health/topics/agents/endocrine

[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310679/

[11] https://www.sciencedirect.com/science/article/pii/S2590161319300948#bib0065

[12] https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813

[13] https://www.nature.com/articles/ncomms9464

[14] https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813

[15] https://pmc.ncbi.nlm.nih.gov/articles/PMC8775814/

[16] https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813

[17] https://academic.oup.com/humupd/article-abstract/20/5/688/2952639?redirectedFrom=fulltext#google_vignette

[18] https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813

[19] https://www.nature.com/articles/ncomms9464

[20] https://www.fertstert.org/article/S0015-0282(17)30535-6/fulltext

[21] https://www.nature.com/articles/ncomms9464

[22] https://pubmed.ncbi.nlm.nih.gov/21151128/

[23] https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0035-1556568