Behavioural, psychiatric, and cognitive phenotypes associated with numbers of repeats of the FRAXE allele on the FMR2 gene.

Background: The FRAXE site on the X-chromosome has a variable number of trinucleotide repeats. The rare condition Fragile XE has >200 repeats, but most X chromosomes have <60 such repeats, with evidence of a bimodal distribution. It is known that when the number of repeats is <60, the repeat number can increase from mother to son, which raises the question as to whether there is an evolutionary advantage in the increased size of these repeats. This paper investigates whether the higher of the <60 repeats are associated with neurocognitive differences among boys in a general population. We hypothesised that although there was previous evidence of a link between higher numbers of repeats in the boys in this population having maternal grandmothers with schizophrenia, there may be cognitive or behavioural advantages to their grandsons of increased levels of repeats.

Methods: We compared 1951 behavioural, psychiatric, and cognitive outcomes of 5060 boys from the Avon Longitudinal Study of Parents and Children (ALSPAC) using a phenome scan.

Results: We found that boys with relatively high levels of repeats (>24) had a higher risk of certain neurocognitive outcomes (P<0.01). Boys with >24 repeats were more likely to report: (a) psychosis-like experiences; (b) increased ability to recognise facial signs of anger; (c) increased risk of eating disorders; (d) increased likelihood of smoking cigarettes and using illicit drugs during adolescence than would be expected by chance. There was no sign of associations with cognitive abilities.

Conclusions: We concluded that there was little evidence that higher levels of the normal range of FRAXE repeats were associated with a difference in cognitive abilities, but there was evidence of increased reports of psychotic-like experiences and other behaviour problems in this group. There was no evidence of evolutionary neurocognitive advantage.