Is eye colour genetic?
Ok, this one is obvious. When kids are first introduced to the concept of genetics in school, they are told that brown is dominant over blue and draw up little punnet squares like this
Incidentally, this is one for my family, which is how I ended up with two daughters with beautiful blue eyes despite being a brown-eyed girl myself. So, why am I looking at this if this if everyone already knows it? Well, I got thinking after the article on designer babies where I mentioned there is a clinic in the US that allows you to choose your babies eye colour. I know that eye colour is determined by the amount and type of melanin in the iris, and as I discussed here genes that affect the production of melanin are the genes which determine skin colour. So, if you choose to have a blue-eyed baby, are you also choosing whiter skin? Because that is even more eugenic than it already seemed.
Firstly, eye colour is not as simple as the little punnet square would have you believe. To start, there’s not only two eye colours, where do we put green, hazel and grey? Then there are cases where two blued-eyed parents have brown eyed children that are presumably not the product of mum having an affair. It turns out eye colour is not a simple monogenic (one gene) thing but involves interactions between many genes. A twin study in Queensland by Zhu et al1 found that about three-quarters of variance in eye colour is down to a single gene and about 18% due to other genes. They put the remaining percentage down to “unique environment (of which most is probably measurement error).
This single gene is known as oculocutaneous albinism type 2 (OCA2), which, as you can probably guess, is also associated with a particular type of albinism. OCA2 codes for a protein known as P protein, named because a mutation in mice causes pink eyes, which affects the pH of the melanosome. Mutations of OCA2 leads to a neutral pH when it should be acidic, which reduces melanin production.2 The variants that cause albinism are severe mutations that result in no functioning protein, but less severe variants result in blue eyes without full-blown albinism.3 There are multiple variants associated with blue eyes, but the most common lies not within OCA2 itself, but within the gene next to it. This region has been shown to promote the expression of OCA2 and as a result, the variant decreases P protein levels fivefold.4 And yes, this blue eye variant is also “strongly associated with paler skin and hair colour”,2 so yes, if you choose your babies eye colour you are also ‘choosing’ their skin colour and no no no no no no NO!
There are other variants in different parts of OCA2 and these variants interact with each other in interesting ways, for example one variant increases the likelihood of green or hazel eyes in people who don’t have the common blue eye variant, but decreases it in people who do.2 Other genes involved in eye colour include interferon regulatory factor 4 (IRF4), where interestingly, one variant is associated with lighter skin and eyes but darker hair, tyrosinase (TYR), which controls the rate of melanin production, and SLC45A2, where variants not only increase the chances of blue eyes but also cause lighter shades of brown.2 These genes interact with each other in ways that give a variety of eye colours. And it is the interactions of these genes that explain how two blue eyes parents can have brown eyed children. Say if mum has the OCA2 variant that causes blue eyes but a brown-eyed TYR and dad has a brown eyed OCA2 but their blue eyes are caused by a TYR variant, their kid ends up with the OCA2 variant from dad and the TYR variant from mum and so have brown eyes.
Taking a combination of the common variants, scientists are able to correctly predict eye colour in Europeans, with an accuracy of 96% for blue or brown eyes, and 82% for ‘intermediate.’5 And yes, these genes are also involved in skin colour, in fact it is thought that lighter eye colours evolved as a side effect of lightening skin as humans moved out of Africa, though one interesting theory is that blue eyes may help protect against seasonal affective disorder in areas where daylight is significantly reduced in winter.2
In summation, yes, eye colour is obviously genetic. And also, the Fertility Institutes essentially allow you to choose lighter or darker skinned babies, and this should absolutely be illegal! I’m surprised I couldn’t find any outrage about this, so if you are in a country where they have a clinic, please join me in complaining
References
1. Zhu G, Evans DM, Duffy DL, et al. A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. Twin Res 2004;7(2):197-210. doi: 10.1375/136905204323016186 [published Online First: 2004/06/01]
2. Duffy D. Genetics of Eye Colour. Encyclopedia of Life Sciences:1-9.
3. Kidd KK, Pakstis AJ, Donnelly MP, et al. The distinctive geographic patterns of common pigmentation variants at the OCA2 gene. Scientific Reports 2020;10(1):15433. doi: 10.1038/s41598-020-72262-6
4. Visser M, Kayser M, Palstra RJ. HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res 2012;22(3):446-55. doi: 10.1101/gr.128652.111 [published Online First: 2012/01/12]
5. Walsh S, Wollstein A, Liu F, et al. DNA-based eye colour prediction across Europe with the IrisPlex system. Forensic Sci Int Genet 2012;6(3):330-40. doi: 10.1016/j.fsigen.2011.07.009 [published Online First: 2011/08/05]