Schizophrenia: 80% ? heritable, not 80% genetic

Schizophrenia: 80% ? heritable, not 80% genetic

ViestiKirjoittaja Psykopatologia » 26.09.2014 13:43

Manchester Psychiatry Society Blog psychiatry | psychology | philosophy

[Oct 21 2011] Chris Meechan http://mancpsychsoc.blogspot.fi/2011/10 ... table.html

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: [VP 0 %; VG 100 %]

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’: [VP 100 %; VG 0 %]

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.

[Lisännyt Pertti Luukkonen]
=> 27.9.2014 9:52

Chris Meechan

Further reading/references
http://www.guardian.co.uk/science/2010/ ... ding-genes
http://www.nature.com/scitable/topicpag ... lity-46889
http://books.google.co.uk/books/about/T ... DQlKwRpfwC
http://www.dialogues-cns.org/brochures/44/pdf/44.pdf
http://books.google.com/books?id=-utBWl ... ia&f=false
http://psych.colorado.edu/~carey/hgss/h ... intro.html
http://archpsyc.ama-assn.org/cgi/conten ... 60/12/1187
http://www.illc.uva.nl/~seop/archives/f ... /heredity/
http://iai.tv/video/richard-bentall-why ... es-you-mad
http://www.schizophrenia.com/research/hereditygen.htm
Joseph, J. (2011). The "Missing Heritability" of Psychiatric Disorders: Elusive Genes or Non-Existent Genes?
(Manuscript submitted for publication.)

Posted 21st October 2011 by Manchester Psychiatry Society
Labels: Bad Science, Genetics, Mental Illness, Myths, Psychiatry, Schizophrenia
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Re: Schizophrenia: 80 % heritable, not 80 % genetic

ViestiKirjoittaja Psykopatologia » 26.09.2014 18:29

Heredity and the Genetics of Schizophrenia http://www.schizophrenia.com/research/hereditygen.htm
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Re: Schizophrenia: 80 % heritable, not 80 % genetic

ViestiKirjoittaja Banana » 26.09.2014 19:50

Ihania kaavioita, nams.
Banana
 

Re: Schizophrenia: 80% ? heritable, not 80% genetic

ViestiKirjoittaja Psykopatologia » 27.09.2014 13:47

Estimating Trait Heritability http://www.nature.com/scitable/topicpag ... lity-46889

By: Naomi R. Wray, Ph.D. (Queensland Institute of Medical Research, Brisbane, Australia) &
Peter M. Visscher (Queensland Institute of Medical Research, Brisbane, Australia) © 2008 Nature Education

Citation: Wray, N. & Visscher, P. (2008) Estimating trait heritability. Nature Education 1(1):29

Genetic variation in a population can result from a variety of things. What are the ways we can estimate trait heritability?
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Quantifying Heritability

Phenotypes that vary between the individuals in a population do so because of both environmental factors and the genes that influence traits, as well as various interactions between genes and environmental factors. Unless they are genetically identical (e.g., monozygotic twins in humans, inbred lines in experimental populations, or clones), the individuals in a population tend to vary in the genotypes they have at the loci affecting particular traits. The combined effect of all loci, including possible allelic interactions within loci (dominance) and between loci (epistasis), is the genotypic value. This value creates genetic variation in a population when it varies between individuals. In fact, heritability is formally defined as the proportion of phenotypic variation (VP) that is due to variation in genetic values (VG).

Genotypes or genotypic values are not passed on from parents to progeny; rather, it is the alleles at the loci that influence the traits that are passed on. Therefore, to predict the average genotypic value of progeny and their predicted average phenotype, investigators need to know the effect of alleles in the population rather than the effect of a genotype. The effect of a particular allele on a trait depends on the allele's frequency in the population and the effect of each genotype that includes the allele. This is sometimes termed the average effect of an allele. The additive genetic value of an individual, called the breeding value, is the sum of the average effects of all the alleles the individual carries (Falconer & Mackay, 1996). According to the principles of Mendelian segregation, one allele from each locus is present in each gamete, and in this way, additive genetic values are passed on from parents to progeny. Indeed, because each offspring receives a different set of alleles from its parents, half of the additive genetic variance in the population occurs within families.

Broad-sense heritability, defined as H2 = VG/VP, captures the proportion of phenotypic variation due to genetic values that may include effects due to dominance and epistasis. On the other hand, narrow-sense heritability, h2 = VA/VP, captures only that proportion of genetic variation that is due to additive genetic values (VA). For definitions and decomposition of components of variation, you can read more about phenotypic variance. Note that often, no distinction is made between broad- and narrow-sense heritability; however, narrow-sense h2 is most important in animal and plant selection programs, because response to artificial (and natural) selection depends on additive genetic variance. Moreover, resemblance between relatives is mostly driven by additive genetic variance (Hill et al., 2008).

Given its definition as a ratio of variance components, the value of heritability always lies between 0 and 1. For instance, for height in humans, narrow-sense heritability is approximately 0.8 (Macgregor et al., 2006). For traits associated with fitness in natural populations, heritability is typically 0.1 – 0.2 (Visscher et al., 2008). [PP]
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Re: Schizophrenia: 80% ? heritable, not 80% genetic

ViestiKirjoittaja Psykopatologia » 28.09.2014 01:40

Älykkyyden peritymisessa on saatu (mm.) broad-heritabiliteetti .48, narrow-heritabiliteetti .34.
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