Investigating genetic links between grapheme–colour synaesthesia and neuropsychiatric traits

Abstract

Synaesthesia is a neurological phenomenon affecting perception, where triggering stimuli (e.g. letters and numbers) elicit unusual secondary sensory experiences (e.g. colours). Family-based studies point to a role for genetic factors in the development of this trait. However, the contributions of common genomic variation to synaesthesia have not yet been investigated. Here, we present the SynGenes cohort, the largest genotyped collection of unrelated people with grapheme–colour synaesthesia ( n = 723). Synaesthesia has been associated with a range of other neuropsychological traits, including enhanced memory and mental imagery, as well as greater sensory sensitivity. Motivated by the prior literature on putative trait overlaps, we investigated polygenic scores derived from published genome-wide scans of schizophrenia and autism spectrum disorder (ASD), comparing our SynGenes cohort to 2181 non-synaesthetic controls. We found a very slight association between schizophrenia polygenic scores and synaesthesia (Nagelkerke's R 2 = 0.0047, empirical p = 0.0027) and no significant association for scores related to ASD (Nagelkerke's R 2 = 0.00092, empirical p = 0.54) or body mass index ( R 2 = 0.00058, empirical p = 0.60), included as a negative control. As sample sizes for studying common genomic variation continue to increase, genetic investigations of the kind reported here may yield novel insights into the shared biology between synaesthesia and other traits, to complement findings from neuropsychology and brain imaging. This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia'.

Synaesthesia and autism: Different developmental outcomes from overlapping mechanisms?

“…There is already evidence of links between synaesthesia and anxiety (Carmichael et al, 2019) and between synaesthesia and PTSD, post-traumatic stress disorder (Hoffman et al, 2019). A possible link with schizophrenia has already been discussed (Tilot et al, 2019). Whatever the mechanisms behind these associations are, they are likely to require a reconceptualization of synaesthesia not just in terms of anomalous experiences (e.g., numbers evoking colour) but as a broader neurocognitive phenotype (Ward & Filiz, 2020).…”

“…schizotypy on some subscales, Banissy et al, 2012, and there is suggestive genetic evidence, Tilot et al, 2019).…”

Language evolution: examining the link between cross-modality and aggression through the lens of disorders

“…In fact, Banissy and colleagues [140] found that synaesthetes score higher on positive schizotypy. In this respect, recent genetic analyses have found a very slight association between SZ polygenic scores and synaesthesia, although no significant association was found between synaesthesia and scores related to ASD [142]. Finally, synaesthesia and TS have also occasionally been found to co-occur in patients, with synaesthetic experiences interacting with, provoking, or being driven by tics and obsessionality [143].…”

Perceptual Gains and Losses in Synesthesia and Schizophrenia

“…Synesthesia is associated with positive, but not negative, schizotypy 53–55 and genetic overlap is suggested. 56 We did not assess schizotypy, which is a potential limitation as higher schizotypy among our synesthetes cannot be ruled out. However, our experiment concerned perception, not positive symptoms; our groups clearly differed in their perceptual experience for letters and/or numbers, which was our focus.…”