A whole-genome scan and fine-mapping linkage study of auditory-visual synesthesia reveals evidence of linkage to chromosomes 2q24, 5q33, 6p12, and 12p12

Julian E Asher, Janine A Lamb, Denise Brocklebank, Jean-Baptiste Cazier, Elena Maestrini, Laura Addis, Mallika Sen, Simon Baron-Cohen, Anthony P Monaco

Research output: Contribution to journalArticle (Academic Journal)peer-review

133 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)279-85
Number of pages7
JournalAmerican Journal of Human Genetics
Volume84
Issue number2
DOIs
Publication statusPublished - Feb 2009

Keywords

  • Genome, Human
  • Sex Characteristics
  • Humans
  • Hallucinations
  • Genetic Markers
  • Chromosomes, Human, Pair 6
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 5
  • Genome-Wide Association Study
  • Chromosomes, Human, Pair 2
  • Genetic Predisposition to Disease
  • Female
  • Male

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