title: The PCSK6 gene is associated with handedness, the autism spectrum, and magical ideation in a non-clinical population.
abstract: Common polymorphisms in the gene PCSK6, whose protein product mediates the development of brain and body asymmetry through the NODAL pathway, have recently been associated with handedness in three studies, making it a key candidate gene for understanding the developmental and expression of human lateralization. We tested the hypothesis that the PCSK6 VNTR polymorphism rs1053972 influences the expression of handedness and aspects of dimensional schizotypy and autism. For a sample of 709 healthy individuals, rs1053972 genotype was significantly associated with categorical measures of handedness, and with dimensional handedness in subsets of the population with high schizotypy and magical ideation or a lack of strong right-handedness. Both findings showed evidence of stronger or exclusive effects among females, compared to males. Genotypes of PCSK6 also showed significant sex-limited associations with magical ideation, a component of positive schizotypal cognition measured using the Schizotypal Personality Questionnaire, and total autism score, measured using the Autism Spectrum Quotient. These results partially replicate previous studies on effects of PCSK6 rs1053972 genetic variation on handedness phenotypes, link the PCSK6 gene with the dimensional expression of neurodevelopmental conditions in healthy individuals, and show that associations of this gene with handedness and psychological phenotypes exhibit evidence of sex-limited effects.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada V5A 1S6.
authors.forename: Kelsey J
authors.initials: KJ
authors.lastname: Robinson
authors.affiliation: Department of Psychology, and Centre for Neuroscience, University of Alberta, 116 St. and 85 Avenue, Edmonton, Alberta, Canada T6G 2R3. Electronic address: phurd@ualberta.ca.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Hurd
authors.affiliation: Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada V5A 1S6.
authors.forename: Silven
authors.initials: S
authors.lastname: Read
authors.affiliation: Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada V5A 1S6. Electronic address: crespi@sfu.ca.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Crespi
mesh_terms: D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000523:psychology; D005260:Female; D007839:Functional Laterality / Q000235:genetics*; D060005:Genotyping Techniques; D006801:Humans; D008273:Magic / Q000523:psychology*; D008297:Male; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D043484:Proprotein Convertases / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012569:Schizotypal Personality Disorder / Q000235:genetics* / Q000523:psychology; D012697:Serine Endopeptidases / Q000235:genetics*; D055815:Young Adult
chemical_list: C080654:PCSK6 protein, human; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Autism; Handedness; Lateralization; PCSK6 gene; Schizotypy; VNTR