title: Supporting the generalist genes hypothesis for intellectual ability/disability: the case of SNAP25.
abstract: Intellectual disability (ID) is an unresolved health care problem with a worldwide prevalence rate of 2-3%. For many years, research into the genetic causes of ID and related disorders has mainly focused on chromosomal abnormalities or X-linked genetic deficits. Only a handful of autosomal genes are known to cause ID. At the same time it has been suggested that at least some cases of ID represent an extreme form of normal intellectual ability and therefore that genes important for intellectual ability in the normal range may also play a role in ID. In this study, we tested whether the autosomal SNAP25 gene, which was previously associated with variation in intellectual ability in the normal range, is also associated with ID. The gene product of SNAP25 is an important presynaptic plasma membrane protein, is known to be involved in regulating neurotransmitter release, and has been linked to memory and learning by its effect on long term potentiation in the hippocampus. Allele frequencies of two genetic variants in SNAP25 previously associated with intellectual ability were compared between a group of 636 ID cases (IQ < 70) and a control group of 361 persons of higher than average intellectual ability. We observed a higher frequency of the putative risk allele of rs363050 (P = 0.02; OR = 1.24) in cases as compared to controls. These results are consistent with a role of SNAP25 in ID, and also support the notion that ID reflects the lower extreme of the quantitative distribution of intellectual ability.
authors: Functional Genomics, Centre for Neurogenomics and Cognitive Research, VU Medical Center and VU University, De Boelelaan 1087, 1081 HV, Amsterdam, The Netherlands. t.rizzi@vumc.nl
authors: T S
authors: TS
authors: Rizzi
authors: G
authors: G
authors: Beunders
authors: P
authors: P
authors: Rizzu
authors: E
authors: E
authors: Sistermans
authors: J W R
authors: JW
authors: Twisk
authors: W
authors: W
authors: van Mechelen
authors: J B
authors: JB
authors: Deijen
authors: H
authors: H
authors: Meijers-Heijboer
authors: M
authors: M
authors: Verhage
authors: P
authors: P
authors: Heutink
authors: D
authors: D
authors: Posthuma
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007360:Intelligence / Q000235:genetics; D007361:Intelligence Tests; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics*
chemical_list: C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25