We first performed a study to explore the effect of CNVs on cognitive performance. On one hand, we reviewed the results of several previous studies exploring the effect of CNVs on general intelligence and analysed their results collectively. And, on the other hand, we explored the effects of CNVs on different aspects of cognition using data collected by ourselves. The study revealed that carrying one of the CNVs that in previous studies have been shown to increase the risk to suffer from schizophrenia impairs learning and short-term memory. The results also suggest that having more genes affected by deletions is related to the same impairments. However, no effect was observed on general intelligence as measured by IQ.
We then performed an study to explore the effect of not only CNVs, but also SNPs, on the volume of the lateral ventricles, that is, the two largest of the cavities inside the brain. The lateral ventricles have been shown to be enlarged not only in patients with schizophrenia, but also in their close relatives that do not suffer from the disease, indicating that there must be one or more genetic alterations that affect both the volume of the lateral ventricles and the risk to suffer disease, but that is/are not enough to cause it. The results of the study revealed that, while the number of psychosis-associated SNPs a person has does not affect the size of their lateral ventricles, having more genes affected by deletions is linked to larger volumes. However, these results were not robust from a statistical point of view, so, in order to confirm their validity, they need to be replicated in an independent sample of individuals.
And, finally, we performed a third study to explore which genes across the genome may affect mismatch negativity (MMN), a brain activity pattern in response to regular and salient stimuli observed in EEG measurements. Patients with schizophrenia and their unaffected relatives have been shown to present impaired MMN responses, meaning that their brain responds more similarly to regular and salient sounds than the brain of healthy people unrelated to psychosis patients do. We thus performed a transcriptome-wide association study, or TWAS, to explore which genes might be implicated in determining MMN responses. The TWAS approach estimates the tendency of each gene of being highly or lowly active in each person looking at the SNPs (single position changes) across the whole genome and tries to establish a connection between that tendency of higher/lower activity for each gene and any biological characteristic like, for example, the MMN response. The TWAS study on MMN revealed that the genes that have an effect on the MMN response tend to be very active in the brain during fetal development, that is, before birth, and silenced in the adult brain. This suggests that the characteristics of the brain that determine how strong its MMN response is going to be in adulthood are mainly shaped before birth.
