Polygenic Risk Scores in Acne Vulgaris

Acne vulgaris (acne) is a chronic inflammatory skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. It is characterized by chronic inflammation of the pilosebaceous unit resulting from bacterial colonization of hair follicles by Propionibacterium acnes, androgen-induced increased sebum production, altered keratinization and inflammation (Lichtenberger et al, 2017). It causes spots and pimples, especially on the face, shoulders, back, neck, chest, and upper arms. The severity of acne varies by the number of non-inflammatory lesions (closed and open comedones), inflammatory lesions (pustules and papules) as well as the residual pathology such as nodules and cysts (Ghodsi et al, 2009; Shalita, 2004).
It affects about 85% of adolescents and young adults (Zouboulis et al, 2005). Disease usually regresses by the age of 25 years, but the incidence of adult acne is significant – it often persists into adulthood, with about 26% of women and 12% of men reporting acne in their 40s (Collier et al, 2008). Acne severity can vary widely, from mild to very severe fulminant disease with systemic involvement, including fever, arthralgias, and lytic bone lesions (Zaenglein, 2018). Irreversible facial scarring occurs in up to 20% of teenagers, with acne vulgaris resulting in a lasting, significant negative impact on emotional and mental health (Williams et al, 2012). These effects include higher rates of anxiety and depression with suicidal ideation, low self-esteem, social isolation and elevated rates of unemployment (Common et al, 2019; Ramrakha et al, 2016).
Studies involving twins have shown that acne is highly heritable, with 81% of the population variance attributed to genetic factors (Bataille et al, 2013). Cross-sectional prevalence studies also indicate a similar genetic contribution, with family history strongly correlating with disease risk and severity (Evans et al, 2005; Ghodsi et al, 2009). Overall, the statistics for heritability are striking and highlight acne vulgaris as a genetically determined complex trait. Genetic studies have revealed associations in biological pathways with overlapping functions concordant with what is known about acne pathogenesis, such as androgen metabolism, inflammation, stem cell fate and tissue remodeling (reviewed by Common et al, 2019). GWAS and rare genetic studies to date indicate a strong link to the tissue microenvironment and tissue remodeling that occurs during development of the mature sebaceous gland, and not to inflammation, which therefore may be considered a secondary event.
Acne is one of the most common diseases in the world, but its pathogenesis remains poorly understood (van Steensel, 2019). No fundamentally new, effective therapeutic approach has been developed since isotretinoin was introduced in 1982. In order to to guide effective, mechanism-targeted treatments, a better understanding of the pathogenesis and molecular mechanisms of acne is needed. The majority of genetic studies to date have focused on severe acne, which makes up 10% of cases (Common et al, 2019). It will therefore be important to replicate and expand studies to include the more prevalent mild-to-moderate acne vulgaris phenotype to confirm that the mechanisms hold true. 
To date, no polygenic risk score has been generated for acne / acne vulgaris.