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

Behavioural, psychiatric, and cognitive phenotypes associated with numbers of repeats of the FRAXE allele on the FMR2 gene
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 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 with 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.
ALSPAC, FRAXE, FMR2, psychosis, substance addiction, smoking, Neurocognition, Eating Disorders
2398-502X
Golding, Jean
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Pembrey, Marcus
0754822a-e6df-4c71-8086-4989663b076c
Clark, Rosie
66150aac-dc74-45cb-a9af-11576ba34f2c
Iles-Caven, Yasmin
1b0bcdde-205d-46c5-91e0-b032f47caf45
Gregory, Steven
cdfbee86-3eb2-4275-818b-64a6ab500235
Ring, Susan
79941daa-7ae8-47f1-beb4-e8560ce12fd8
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Suderman, Matthew
404b6081-e1ce-4419-af87-3e19bad2322e
Golding, Jean
3bc7cd2b-1d28-4160-8624-a12422a12bca
Pembrey, Marcus
0754822a-e6df-4c71-8086-4989663b076c
Clark, Rosie
66150aac-dc74-45cb-a9af-11576ba34f2c
Iles-Caven, Yasmin
1b0bcdde-205d-46c5-91e0-b032f47caf45
Gregory, Steven
cdfbee86-3eb2-4275-818b-64a6ab500235
Ring, Susan
79941daa-7ae8-47f1-beb4-e8560ce12fd8
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Suderman, Matthew
404b6081-e1ce-4419-af87-3e19bad2322e

Golding, Jean, Pembrey, Marcus, Clark, Rosie, Iles-Caven, Yasmin, Gregory, Steven, Ring, Susan, Ennis, Sarah and Suderman, Matthew (2024) Behavioural, psychiatric, and cognitive phenotypes associated with numbers of repeats of the FRAXE allele on the FMR2 gene. Wellcome Open Research. (In Press)

Record type: Article

Abstract

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 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 with 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.

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FRAXE NEUROCOG V8 16.3.24 - Accepted Manuscript
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Accepted/In Press date: 11 May 2024
Keywords: ALSPAC, FRAXE, FMR2, psychosis, substance addiction, smoking, Neurocognition, Eating Disorders

Identifiers

Local EPrints ID: 491668
URI: http://eprints.soton.ac.uk/id/eprint/491668
ISSN: 2398-502X
PURE UUID: 81adf4af-8087-4d94-9ae0-99e6c5b603a5
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869

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Date deposited: 03 Jul 2024 09:52
Last modified: 01 Aug 2024 04:01

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Contributors

Author: Jean Golding
Author: Marcus Pembrey
Author: Rosie Clark
Author: Yasmin Iles-Caven
Author: Steven Gregory
Author: Susan Ring
Author: Sarah Ennis ORCID iD
Author: Matthew Suderman

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