Summary
I want to focus on how we can use the failure of Genome Wide Association Studies (GWAS) to produce strong genetic associations to revisit the traditional understanding of schizophrenia as a highly heritable condition.
Highlights
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Doesn’t the heritability of schizophrenia, which is estimated to be ~80%, constitute strong evidence of the genetic causation of schizophrenia, that schizophrenia is “80% genetic”? Not quite. I think schizophrenia is 80% genetic only in the technical sense of heritability, but not in any other sense
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We cannot, for example, use schizophrenia’s 80% heritability at the population level to say, “For a randomly selected person with schizophrenia in this population, 80% of their etiology is genetic in nature.” The heritability statistic applied to an individual has no meaning
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A statistical investigation focused on variation is not necessarily informative about the causal mechanisms that give rise to any individual instance of a phenomenon
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Estimates of heritability using twin studies also rely on the assumption that environments encountered by identical twins are no more similar than environments encountered by fraternal twins. This is not entirely true either. For example, “It starts in the womb: while fraternal twin embryos are always connected to their mother via two unique placentas, identical twins most often (but not always) share a single placenta. This means that, beginning soon after conception, identical twins typically have more similar access to nutrients, oxygen, and other factors than do fraternal twins” (Moore and Shenk, 2017) Again, this may not invalidate the heritability estimates entirely, but it can certainly inflate the estimates inaccurately. This assumption is particularly important for schizophrenia since intrauterine events such as infections during pregnancy, maternal inflammation, maternal nutritional deficiencies, obstetric emergencies, maternal use of cannabis, etc. are believed to be relevant to schizophrenia risk.
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the genes associated with schizophrenia are not specific to schizophrenia. We can think of them as conferring a nonspecific vulnerability to psychopathology rather than conferring a risk for schizophrenia per se
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The impact of individual genes on risk for psychiatric illness is small, often nonspecific, and embedded in complex causal pathways. The phrase “a gene for…” and the preformationist concept of gene action that underlies it are inappropriate for psychiatric disorders.
Cita de Ken Kendler