Besides entanglement (traits N and A are partially entangled in a population, as lack of the one trait implies presence of the other), the issue of genetic heterogeneity is important. Thus, in one family of particular NPA types an allele coding for the inhibition of aggression may increase the risk of SCZ, while in another family the allele may be silent.
So, the best studies of single gene susceptibility would be that of large families. Next best, would be in relatively homogeneous "habitancies", i,e., having a high prevalence of a particular NPA type, like NP.
Large global studies, or meta-analyses, would be the least specific, as they would blend the results of studies where a single gene could be a risk factor in some families but not in others.
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