The Complex Genetic Architecture Underlying Human Differences

You’d be forgiven for assuming your height has nothing to do with the curl of your hair or how flexible you are, but physical traits can sometimes have unexpected connections.

Last week at the annual meeting of the American Society of Human Genetics in San Francisco, 23andMe’s Principal Scientist and Statistical Geneticist Nick Eriksson presented findings from our database about 300 new genetic associations with various physical traits.

It’s not surprising that a single trait — having a unibrow, for instance — might be influenced by any number of different genetic variants. In the case of unibrow, we’ve found more than 50 genetic variants associated with the trait. It is also well known that genetic variants can be associated with multiple traits and conditions. For example, variants in the PAX3 gene have independent associations with unibrow, whether you’ve got a chin dimple, or upper back hair.

It’s the sheer volume of newly discovered associations that is so surprising. Beyond that, the work is both interesting and informative in what it says about the web of connections between these traits and conditions. These associations shed new light on how genes and gene expression may influence those conditions and traits as well as certain diseases.

While there may be some novelty in finding associations with traits like breast size, sometimes these associations tell us something very important. In the case of breast size there’s a connection with breast cancer, for instance. And these associations can also lead us to new ways of thinking about how certain conditions develop.

Nick’s presentation was meant in part to simply put out there some of the findings we’ve made.

These findings were made because our customers answered questions concerning easily identifiable physical traits, such as whether they’re bald, can easily touch their toes and whether their ring finger is longer than their index finger. Comparing this data with their genetics we were able to see connections that could give us greater understanding of links between these seemingly unrelated traits.

Looking at the PAX3 gene again, which contains variants that influence normal facial development, there are variants that are also associated with a syndrome that leads to deafness, facial abnormalities and skin pigmentation irregularities. Variants in another gene HOXD, which is essential for hand and foot development, are also associated with some severe deformities. And variants in the EDAR gene — which influence the baldness, the straightness of your hair and the amount of back hair you have — are also associated with ectodermal dysplasias, that effects the development of hair, nails, skin and teeth. So understanding these associations with common but complex traits can also provide insight into rare disorders and conditions.

People fuel 23andMe’s engine of discovery because they choose to answer a few questions about themselves. This has allowed us to answer questions about genetics and it has also allowed us to study over 1,000 different traits and conditions, many of which have never been analyzed in such a large scale. What we’ve gleaned from this data so far is a picture of the complex genetic architecture underlying human differences and point us in the right directions for future study.