The use of the twin model to investigate the genetics and epigenetics of skin diseases with genomic, transcriptomic and methylation data

Abstract

Twins have always fascinated medical research even before the discovery of DNA and the understanding of the differences between identical and non-identical twins. Dermatology with the benefit of being able to visualize phenotypes was one of the first specialities reporting on the fascinating concordance in identical (MZ) twins in the 1920's. Over the last 20 years, the heritability of skin diseases using twins has been clearly demonstrated, across a wide variety of traits including melanoma, polymorphic light eruption, psoriasis, eczema and acne. Other rarer diseases have also been shown to have a significant genetic basis such as lupus, sarcoidosis and lichen sclerosus. Following evidence of heritability for many skin disease the next step was Genome-Wide Association Studies (GWAS) which are uncovering new genes in large twin cohorts. The twin model is also ideal for the new field of epigenetics, investigating subtle differences in DNA methylation within discordant MZ pairs for a disease, as well as differences in CNVs. Twins are also valuable for examining differences in gene function via RNA expression in twins discordant for a skin trait or disease.

Heritability of psoriasis in a large twin sample

“…The classical twin design assumes that monozygotic (MZ) twins not only share all their genes, but also their upbringing and early environment, whereas dizygotic (DZ) twins share, besides their upbringing and early environment, on average half of their segregating genes. Heritability is estimated by comparing concordance of disease between MZ and DZ pairs …”

Evaluation of candidal colonization and specific humoral responses against Candida albicans in patients with psoriasis

“…The exact etiology of psoriasis remains unknown, but it is believed that a combination of several factors such as genetic predisposition and environmental and immunological factors contribute to the development of this disease . Among environmental factors, various microorganisms such as viruses (retroviruses, papillomaviruses, and endogenous retroviruses), bacteria ( Staphylococcus aureus , Streptococcus pyogenes ), and fungi ( Candida s pp., Malassezia spp.)…”

DNA methylation of the filaggrin gene adds to the risk of eczema associated with loss‐of‐function variants

“…4,5 Epigenetic regulatory mechanisms are mitotically heritable and can alter gene expression without changing the DNA sequence. 6 DNA methylation, widely studied in epidemiological investigations due to practical and biological reasons 7,8 , along with histone modifications are important epigenetic marks that work hand-in-hand on influencing disease expression.…”