Case study 3: Search for a phenotype (non-melanoma skin cancer)

With a known phenotype, you may wish to find studies focusing on it as well as variants and genes that are associated with the phenotype. In this case study we look at how you can find studies, variants and genes associated with the phenotype “non-melanoma skin cancer”.

To find studies looking at the phenotype, as well as associated genes and variants you can search for “non-melanoma skin cancer” in the GWAS Catalog (Figure 13).

There are several studies in GWAS that focus on this trait. They identify many SNPs associated with non-melanoma skin cancer or more specific sub-types, including three in MC1R.

Another place to find information about phenotypes is Ensembl (Figure 14). Since Ensembl is not restricted by method type, it includes phenotype associations from GWAS, as well as sources such as ClinVar, OMIM, Orphanet and COSMIC, which may be associated with either the variant or the gene.

For detailed descriptions of phenotypes, you can go to OMIM. As well as clinical descriptions, OMIM also describes the biological and molecular functions of genes associated with the phenotypes along with references.

In case study 2 we saw how you can use Ensembl, UniProt and PDBe to explore a gene or variant in more detail. Open Targets is another resource that you can use. It was originally designed for validating potential drug targets but is also useful for getting an overview of the data and features associated with a phenotype or gene.

As we saw in the GWAS Catalog, SNPs in MC1R are associated with non-melanoma skin cancer. If we look at this gene in Open Targets we can see that it is also associated with hair colour. Indeed people with red hair and freckles often have certain SNPs in MC1R.