title: Intelligence in Williams Syndrome is related to STX1A, which encodes a component of the presynaptic SNARE complex.
abstract: Although genetics is the most significant known determinant of human intelligence, specific gene contributions remain largely unknown. To accelerate understanding in this area, we have taken a new approach by studying the relationship between quantitative gene expression and intelligence in a cohort of 65 patients with Williams Syndrome (WS), a neurodevelopmental disorder caused by a 1.5 Mb deletion on chromosome 7q11.23. We find that variation in the transcript levels of the brain gene STX1A correlates significantly with intelligence in WS patients measured by principal component analysis (PCA) of standardized WAIS-R subtests, r = 0.40 (Pearson correlation, Bonferroni corrected p-value = 0.007), accounting for 15.6% of the cognitive variation. These results suggest that syntaxin 1A, a neuronal regulator of presynaptic vesicle release, may play a role in WS and be a component of the cellular pathway determining human intelligence.
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Gao
authors.forename: Ursula
authors.initials: U
authors.lastname: Bellugi
authors.forename: Li
authors.initials: L
authors.lastname: Dai
authors.forename: Debra L
authors.initials: DL
authors.lastname: Mills
authors.forename: Eric M
authors.initials: EM
authors.lastname: Sobel
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lange
authors.forename: Julie R
authors.initials: JR
authors.lastname: Korenberg
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D017729:Presynaptic Terminals / Q000737:chemistry; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000032:analysis; D050600:SNARE Proteins; D050827:Syntaxin 1 / Q000235:genetics*; D018980:Williams Syndrome / Q000178:diet therapy* / Q000503:physiopathology / Q000523:psychology*
chemical_list: D012333:RNA, Messenger; D050600:SNARE Proteins; C494212:STX1A protein, human; D050827:Syntaxin 1