Yes, our genes affect everything we do, from educational attainment to health, but they are only a contributing factor

The cost of DNA sequencing continues to fall, and the scale and reach of genetic research continues to grow with it. We can use genetics to study not just health and fundamental biology but many things humans do education, behaviours, parenting skills leading to interesting scientific papers and sometimes breathless headlines in the mainstream press. But what can DNA really tell us about our potential and our behaviours? Is the science sound? How should society use this knowledge?

Broadly speaking, yes, the science is sound. The human genome varies slightly between all of us. Once you study enough people often more than 10,000 genetic variation will have some kind of impact on nearly anything we do. There are many factors that contribute to complex measurements or behaviours, such as performance in school, so lots of weak effects can add up to a substantial impact. However, the degree to which this variation affects individuals can be quite different depending on what you are looking at. For example, up to 80% of what determines height lies in our genetic code, but only 30% of the causes of multiple sclerosis are genetic. Reasonably complex outcomes, such as the score in an IQ test, or whether you stay in education beyond the age of 16, also have quite substantial genetic components between 50 to 60%.

However, these numbers can easily be misinterpreted the average height is good 3-4cm taller in South Korea than North Korea, despite near identical genetics between the two parts of the Korean peninsula. These studies only report the variation within a population and its context, and not absolutes. In this case, presumably better nutrition in South Korea shifts the mean height across near everyone. Similarly, many more people in the UK now stay in education beyond 16 compared to 200 years ago, but our genetics hasnt changed in that period. This context-dependent expression of our genetic variation is important; each persons genome is fixed at birth, but the fixed nature of the genome and the 50% of variation in educational attainment explained by genetics doesnt mean schooling or education is pointless; a child who doesnt go to school will not perform well in tests, however good their genome predicts them to be, just as a child with poor nutrition will be shorter in height.

So how can we use genetics? For researchers, understanding the biology behind these traits is inherently interesting and represents the potential for new therapeutics, for example, for depression. But one can also use genetics more directly. Its unlikely that we will use it to predict particular attributes on individuals. If you want to know how well someone will perform at GCSE, or go onto university, you should give them a mock exam; testing their genome to provide a prediction will always be less accurate.

There is another useful feature of genetics we can use. Genetic variants are randomly distributed in the population because each parent only passes on half of their genome to their children, meaning that a childs genome is almost a perfect shuffle of his or her grandparents genomes. The choice of which variant you get from your grandparents is almost perfectly random, and inside of well mixed populations (for example, European ancestry in Europe), the distribution of variants is remarkably random, with little concern to wealth, position or other societal effects. This near perfect shuffling means that we can use each variant like a miniature randomised control trial, akin to a drug trial (there is nice animation on this technique here).

This can untangle some complex cause vs correlation questions. To take an example from medicine, higher levels of good cholesterol (HDL) are present in healthy people who have fewer heart attacks. But does higher HDL reduce the chance of suffering a heart attack, or does being healthy mean fewer heart attacks and higher HDL?

For a long time, the evidence pointed to the beneficial properties of good cholesterol, and billions of dollars were invested in drugs to raise HDL levels. However, by using genetic variants, randomly distributed between people with healthy or unhealthy lifestyles and which systematically slightly lowered or slightly raised good cholesterol, scientists found that HDL levels alone do not affect the risk of heart attacks a result also confirmed by a multi-million dollar drug trial.

Imagine if we substituted good cholesterol with another feature, for example performance in phonics tests in early life, and heart attacks for performance in English exams. Do better phonics in early life give rise to better GCSE English results? Or do more general correlations to other behavioural features give rise to both? Or the propensity to take risks and use drugs? These are the kinds of correlations that genetics will allow us to unpick in the future.

As a geneticist, I am both excited and concerned about how this will play out. Most people understand the unchanging nature of DNA. Outside the scientific discourse, DNA has come to mean the core values of something often used in reference to a business or a sports team (transparency is in our DNA). This oversteps the science and the contextual nature where differences in DNA interact with the environment. The child born with the best ever DNA cards for educational attainment will not magically be transported to university aged 19 without working hard at school. Short-sightedness has a strong genetic component, but prescription glasses (environment in the parlance of geneticists) mitigate the majority of this trait. We are a combination of nature and nurture, and whatever percentage nature is quoted, it should be seen in the context of a particular society and environment that we can influence.

Secondly, I worry that the visible differences between people skin colour, facial features, hair colour, which are also largely genetic will be incorrectly combined with growing understanding of genetics on behaviours to produce scientifically incorrect and societally damaging results. Despite variation in skin colour being largely genetic and educational attainment having substantial genetic component, genetics does not explain why we have fewer young black British adults going into tertiary education. Skin colour genetics covers a tiny proportion of the genome, and it stands apart from the genetics of educational attainment; the two are independent of each other. Talking about genetics without helping people to navigate this space will allow modern racism to flourish.

Just as 100 years ago we refined our understanding that eating fruit and vegetables regularly was good for everyone with the discovery of vitamins, nowadays we can refine our understanding of genetics and genomics to improve education and health for everyone.

We should embrace the use of DNA to probe the complex features of humans. However, we must remember that although DNA sequencing is one of the many useful tools for understanding our complex world, its not a way of justifying the complex differences we see around us from behaviour to inequality. DNA is not our destiny; it is just a very useful tool.

Read more: https://www.theguardian.com/science/2018/apr/05/dna-sequencing-educational-attainment-height

A two minute primer on mendelian randomisation

Professor George Davey Smith gives us a brief overview of Mendelian randomisation. What is it, and how does it help us to understand the causal impact of behaviours, such as smoking, on health?
For more information, see: https://academic.oup.com/hmg/article/23/R1/R89/2900899

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