Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.
OBJECTIVE
Autism displays a remarkably high heritability but a complex genetic etiology. One approach to identifying susceptibility loci under these conditions is to define more homogeneous subsets of families on the basis of genetically relevant phenotypic or biological characteristics that vary from case to case.


METHODS
The authors performed a principal components analysis, using items from the Autism Diagnostic Interview, which resulted in six clusters of variables, five of which showed significant sib-sib correlation. The utility of these phenotypic subsets was tested in an exploratory genetic analysis of the autism candidate region on chromosome 15q11-q13.


RESULTS
When the Collaborative Linkage Study of Autism sample was divided, on the basis of mean proband score for the "savant skills" cluster, the heterogeneity logarithm of the odds under a recessive model at D15S511, within the GABRB3 gene, increased from 0.6 to 2.6 in the subset of families in which probands had greater savant skills.


CONCLUSIONS
These data are consistent with the genetic contribution of a 15q locus to autism susceptibility in a subset of affected individuals exhibiting savant skills. Similar types of skills have been noted in individuals with Prader-Willi syndrome, which results from deletions of this chromosomal region.
Nurmi
Erika L
EL
Medical Scientist Training Program, Vanderbilt University, Nashville, TN 37232-0615, USA.
Dowd
Michael
M
Tadevosyan-Leyfer
Ovsanna
O
Haines
Jonathan L
JL
Folstein
Susan E
SE
Sutcliffe
James S
JS
D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D005163:Factor Analysis, Statistical; D005260:Female; D015870:Gene Expression / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism
D018079:Receptors, GABA