Friday, August 14, 2020

Genetic Prediction of Schizophrenia via Polygenic Risk Score Has No Clinical Utility

 A new study from Schizophrenia Bulletin tested various risk factors on a group of individuals in a Netherlands. In addition to other risk factors, they used Polygenic Risk Score (PRS) developed from previous studies. This summarizes the results:

We calculated the relative contribution of each (group of) risk factor(s) to the variance in (change in) mental health. In the combined model, familial and environmental factors explained around 17% of the variance in mental health, of which around 5% was explained by age and sex, 30% by social circumstances, 16% by pain, 22% by environmental risk factors, 24% by family history, and 3% by PRS for schizophrenia (PRS-SZ). Results were similar, but attenuated, for the model of mental health change over time. Childhood trauma and gap between actual and desired social status explained most of the variance.

 This is a weak result all around, but particularly bad was the PRS which had a predictive success of 0.5 % (3% of 17%). Thus, just knowing a person's age and sex was almost twice as predictive as the PRS. If the person had a history of pain or other medical complaints, that alone was 4 times more predictive for schizophrenia. This is simply a dismal failure and the continued hope that this will be good enough to be clinically useful is little more than wishful thinking. Realistically, to be clinically useful, it would have to be 25 to 50 times better than this and I am guessing it has come close to peaking.

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