Gene × gene interaction in shared etiology of autism and specific language impairment.
BACKGROUND
To examine the relationship between autism spectrum disorders (ASD) and specific language impairment (SLI), family studies typically take a comparative approach where families with one disease are examined for traits of the other disease. In contrast, the present report is the first study with both disorders required to be present in each family to provide a more direct test of the hypothesis of shared genetic etiology.


METHODS
We behaviorally assessed 51 families including at least one person with ASD and at least one person with SLI (without ASD). Pedigree members were tested with 22 standardized measures of language and intelligence. Because these extended families include a nonshared environmental contrast, we calculated heritability, not just familiality, for each measure twice: 1) baseline heritability analysis, compared with; 2) heritability estimates after statistically removing ASD subjects from pedigrees.


RESULTS
Significant increases in heritability on four supra-linguistic measures (including Pragmatic Judgment) and a composite language score but not on any other measures were observed when removing ASD subjects from the analysis, indicating differential genetic effects that are unique to ASD. Nongenetic explanations such as effects of ASD severity or measurement error or low score variability in ASD subjects were systematically ruled out, leaving the hypothesis of nonadditive genetics effects as the potential source of the heritability change caused by ASD.


CONCLUSIONS
Although the data suggest genetic risk factors common to both SLI and ASD, there are effects that seem unique to ASD, possibly caused by nonadditive gene-gene interactions of shared risk loci.
Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA. bartletc@ccri.net
Christopher W
CW
Bartlett
Judy F
JF
Flax
Zena
Z
Fermano
Abby
A
Hare
Liping
L
Hou
Stephen A
SA
Petrill
Steven
S
Buyske
Linda M
LM
Brzustowicz
D000293:Adolescent; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology* / Q000235:genetics*; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006801:Humans; D007360:Intelligence; D007805:Language Development Disorders / Q000453:epidemiology* / Q000235:genetics*; D016013:Likelihood Functions; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D055815:Young Adult
C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins