Thursday, 20 October 2011

Schizophrenia is (arguably*) 80% heritable; it is not 80% genetic


The misconception:  Heritability is the measure of the extent to which genes cause a particular trait within an individual and is therefore a measure of causation.

The truth: Heritability is a measure of the extent to which variation of a phenotype between individuals in a population is due to differences in their genes. It is therefore a measure of variation not causation.

The Implications: When a mental disorder is said to be x% heritable, people wrongly assume it is x% genetic and 100-x% environmental, thus missing the point that both play a crucial and complex role.





Genetics has flourished in the latter half of the twentieth century, and with good reason. It has revolutionised Biology and Medicine and it has even changed our perception of ourselves as humans, with Watson and Crick’s discovery of DNA replacing the ‘vital spirit’ or ‘soul’ of life. Genetics has also played at least some kind of role in mental illnesses such as Schizophrenia and Bipolar. In fact Schizophrenia is commonly (although debatably*) quoted as being 80% heritable. But what does this actually mean?

If, like me, you thought it meant that 80% of an individual’s disorder is caused by genes, you should probably keep reading. 

You are wrong. 

Many people, scientists, even geneticists think that the extent to which a disorder is heritable (given as a percentage) is the extent to which it is caused by genes. Nope. In fact, a trait can be 100% heritable but mainly caused by environmental factors. It can even be 100% genetic but nearly 0% heritable. 

Here is why:  
                                             
Heritability is formally defined as “the proportion of phenotypic variation (VP) that is due to variation in genetic values (VG)”. In other words, it is a measure of the extent to which differences in a trait between individuals in a population are due to the genetic differences of those individuals.It is NOT the extent to which an individual’s trait is caused by their genes. So we are talking about populations not individuals. A heritability of .80 informs us that, on average, about 80% of the variation (differences) within a population that we observe in, say, Schizophrenia may be attributable to variation in genes.

Ok, so how can the environment be the main cause of a 100% heritable trait? Well it’s because heritability is affected by the variation in an environment. Let’s borrow a thought experiment courtesy of Professor Richard Bentall: 

Imagine a world where everybody smokes 200 cigarettes a day. In this worrying scenario, the environmental factors are controlled (there is no environmental variance), therefore the only difference between whether a person gets lung cancer or not has to be due to individual differences in genes (it cannot be whether someone smokes or not since everyone’s at it). As a result heritability is 100%. Here is the important (non)implication for causality; we would not argue that the genes caused the lung cancer, the smoking caused the lung cancer. The genes caused the variation between people in a situation where everyone shared the same nicotine-obsessed environment. Hence the only explanation for differences between individuals is the genes. 

Here’s another example, in reverse from Jay Joseph’s ‘The Gene Illusion’:

The phenotype of having two eyes is 100% inherited but because most of the variation in the population is due to environmental factors (Teddy Roosevelt lost an eye while boxing), it has a heritability of close to 0**. This is because cases where people have one or no eyes are normally due to an environmental accident rather than their genes (exceptions include Anophthalmia, a congenital disorder).

Back to the world of Psychiatry and our .80 heritability for Schizophrenia: This does not mean Schizophrenia is 80% genetic and the remaining 20% is caused by environmental factors. The point is we have to be very careful when looking at heritability in a population, as it is very misleading if not properly understood. In fact, many argue that the entire nature vs nurture dichotomy is somewhat misguided. Due to the complex dynamic interaction of genes and environment it is not useful for us to try to separate the two since “for most traits we know about, genetic and environmental influences are inexorably intertwined.” Some, such as Jay Joseph, question the very use of heritability in Psychiatry research at all – though most would disagree.

I wanted to write this piece, because I felt like, as a medical student, Schizophrenia is always referred to as a mainly genetic disorder and that somehow because of a genetic involvement, environment is unimportant. Interestingly, in the days of Freud, the problem was reversed, with the emphasis on the ‘Schizophrenic mother’ and a rejection of genetic factors. Perhaps now is the time for a true realization of the important roles both play in our lives and the potential dangers of neglecting either our nature or our nurture.

* Many sources show heritability of Schizophrenia at around 50%. Bentall quotes Jay Joseph’s paper (which is waiting to be published) stating heritability is at 24% using the best and most rigorous studies.
** 'Heritability' and 'Inherited' have very different meanings. Heritability is as defined above. Inherited refers to heredity which is the genetic transmission of characteristics from parent to offspring.

Chris Meechan

Further reading/references
Joseph, J. (2011). The "Missing Heritability" of Psychiatric Disorders: Elusive Genes or Non-Existent Genes? (Manuscript submitted for publication.)

6 comments:

  1. Very insightful article! The 'heritability as causation' misconception is rampant. Thank you!

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  2. well done! medical students these days understand statistics much better than they did back in the 1980's! ...& yet statistical understanding must have substantial heritability:)

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  3. Thanks very much. Unfortunately I had to intercalate in psychology for a year to get any knowledge of statistics. The only stats we have been taught as medics (in my first 2 years at least) has been an online tutorial, with a quiz that counts for nothing. It's comical considering you can't understand a quantitative paper without it!

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  4. Thanks for the article, currently studying psychology and your article was helpful for a genetics essay and yes we do alot of statistics and investigation methods in the degree.

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  5. I have to think about it a bit more but I believe you are right. Good article!

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