Scientists Uncover Gene Variant Associated with Freckles, Blue Eyes and Brown Hair

Do you have blue eyes? What about brown hair, freckles and sensitivity to the sun? Scientists may have uncovered a genomic variant strongly associated with these traits. The findings could reveal a bit more about human pigmentation and allow scientist to better understand how certain genes are expressed.

People with ancestors from geographic locations further from the equator, such as Iceland, are more likely to have less pigment in their skin, hair and eyes. Although people with reduced pigment are more sensitive to the sun, they also are able to more easily draw upon sunlight to generate vitamin D3, a nutrient that's essential for healthy bones. This trait may be detrimental in tropical locations like Florida but in places that are dark for part of the year, like Finland, this particular adaptation is extremely useful.

In order to find out a little bit more about human pigmentation, the researchers analyzed data from a genome-wide association study (GWAS) of 2,230 Icelanders. It compared hundreds of thousands of common differences across individuals' DNA to see if any of those variants were associated with a known trait.

"Genes involved in skin pigmentation also have important roles in human health and disease," said Dan Kastner, one of the researchers, in a news release. "This study explains a complex molecular pathway that may also contribute insights into skin diseases, such as melanoma, which is caused by the interaction of genetic susceptibility with environmental factors."

The researchers focused on the interferon regulatory factor 4 (IRF4) gene, which was previously associated with immunity. They found that the IRF4 gene is expressed at high levels only in lymphocytes, a type of white blood cell that's important in the immune system, and in melanocytes, which are specialized skin cells that make the pigment melanin.

In the end, the scientists discovered that a variant in a non-coding, enhancer region that regulates the IRF4 gene is associated with the combined trait of sunlight sensitivity, brown hair, blue eyes and freckles. This finding in particular places IRF4 among more than 30 genes that are now associated with pigmentation, including a gene variant previously found in people with freckles and red hair.

More research needs to be conducted in order to determine the mechanism by which IRF4 is involved in how melanocytes respond to UV damage, which can induce freckling as is linked to melanoma. Yet this latest study does reveal further insight into human pigmentation. This, in turn, could greatly help in future studies.

The findings are published in the journal Cell.