Incorporating language phenotypes strengthens evidence of linkage to autism

We investigated the effect of incorporating information about proband and p arental structural language phenotypes into linkage analyses in the two reg ions for which we found the highest signals in our first-stage affected sib ling pair genome screen: chromosomes 13q and 7q. We were particularly inter ested in following up on our chromosome 7q finding in light of two prior re ports of linkage of this region to developmental language disorder, since o ne of the diagnostic criteria for autism is absent or abnormal language dev elopment. We hypothesized that if the language phenotype were genetically r elevant to linkage at the chromosome 7q locus, then incorporating parents p henotypes would increase the signal at that locus, and most of the signal w ould originate from the subset of families in which both probands had sever e language delay. The results support these hypotheses. The linkage signals we obtained on chromosome 7q as well as at least one signal on chromosome 13q are mainly attributable to the subgroup of families in which both proba nds had language delay. This became apparent only when the parents' history of language-related difficulties was also incorporated into the analyses. Although based on our data, we were not able to distinguish between epistas is or heterogeneity models, we tentatively concluded that there may be more than one autism susceptibility locus related to language development. (C) 2001 Wiley-Liss, Inc.