title: A whole-genome scan and fine-mapping linkage study of auditory-visual synesthesia reveals evidence of linkage to chromosomes 2q24, 5q33, 6p12, and 12p12.
abstract: Synesthesia, a neurological condition affecting between 0.05%-1% of the population, is characterized by anomalous sensory perception and associated alterations in cognitive function due to interference from synesthetic percepts. A stimulus in one sensory modality triggers an automatic, consistent response in either another modality or a different aspect of the same modality. Familiality studies show evidence of a strong genetic predisposition; whereas initial pedigree analyses supported a single-gene X-linked dominant mode of inheritance with a skewed F:M ratio and a notable absence of male-to-male transmission, subsequent analyses in larger samples indicated that the mode of inheritance was likely to be more complex. Here, we report the results of a whole-genome linkage scan for auditory-visual synesthesia with 410 microsatellite markers at 9.05 cM density in 43 multiplex families (n = 196) with potential candidate regions fine-mapped at 5 cM density. Using NPL and HLOD analysis, we identified four candidate regions. Significant linkage at the genome-wide level was detected to chromosome 2q24 (HLOD = 3.025, empirical genome-wide p = 0.047). Suggestive linkage was found to chromosomes 5q33, 6p12, and 12p12. No support was found for linkage to the X chromosome; furthermore, we have identified two confirmed cases of male-to-male transmission of synesthesia. Our results demonstrate that auditory-visual synesthesia is likely to be an oligogenic disorder subject to multiple modes of inheritance and locus heterogeneity. This study comprises a significant step toward identifying the genetic substrates underlying synesthesia, with important implications for our understanding of the role of genes in human cognition and perception.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. j.asher@imperial.ac.uk
authors.forename: Julian E
authors.initials: JE
authors.lastname: Asher
authors.forename: Janine A
authors.initials: JA
authors.lastname: Lamb
authors.forename: Denise
authors.initials: D
authors.lastname: Brocklebank
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Cazier
authors.forename: Elena
authors.initials: E
authors.lastname: Maestrini
authors.forename: Laura
authors.initials: L
authors.lastname: Addis
authors.forename: Mallika
authors.initials: M
authors.lastname: Sen
authors.forename: Simon
authors.initials: S
authors.lastname: Baron-Cohen
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Monaco
mesh_terms: D002874:Chromosome Mapping / Q000379:methods*; D002881:Chromosomes, Human, Pair 12; D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006212:Hallucinations / Q000235:genetics*; D006801:Humans; D008297:Male; D012727:Sex Characteristics
chemical_list: D005819:Genetic Markers