Approved Research

Variability-controlling quantitative trait loci (vQTL) for intelligence and their association with increased risk for severe psychiatric disorders

Lay summary

Aims

The first aim of our study is the identification of genetic variants linked to the degree of variability (vQTL) for intelligence. At population level vQTL do not influence mean values of a trait - for example intelligence - but are related to the degree of heterogeneity of individual values.

The second aim of our project is to test the hypothesis that vQTL for intelligence are associated with risk for two groups of severe psychiatric disorders: psychotic (e.g. schizophrenia) and affective disorders (e.g. bipolar disorder, recurrent depression).

Scientific rationale

Complex traits (like intelligence) and disorders (like psychotic or affective disorders) are due to genetic and environmental factors and their interactions. Two types of genetic factors may influence quantitative traits like intelligence (usually measured by the intelligence quotient - IQ) The first ones are quantitative trait loci (QTL) or mean-controlling factors. The presence of such factors changes the values of the trait in a specific, predictable manner. For example, some QTL are associated with higher IQ and others with lower IQ. The second type of genetic factors - vQTL - are associated with the degree of variation of the trait i.e. the heterogeneity of values in a population. Their action is supposed to involve interaction with other genetic (e.g. QTL) or environmental factors. Through such interactions vQTL will non-specifically potentiate the effect of multiple factors, some increasing and some others decreasing the values of a trait. Thus, vQTL will not result in a change in the mean value of the trait but in a higher proportion of extreme values, both low and high, corresponding to a higher heterogeneity in the population.

The existence of vQTL for intelligence has not been tested yet. We make the hypothesis that some of them exert their effect by influencing brain development. Because both psychotic and affective disorders have been associated with abnormal brain development, we expect vQTL for intelligence to be more frequent in subjects suffering from these disorders.

Project duration

We expect to be able to analyze and publish the results in 12 months from receiving the data.

Public health impact

If our hypotheses are confirmed, this study might have important consequences for the understanding of the determinants of important outcomes such as intelligence, schizophrenia and bipolar disorders. Furthermore, it could lay the bases for identifying at risk subjects in which preventive measures might be more efficient.