Family-based analyses were first performed using FBAT, which allows for rapid calculation of statistics under additive, dominant and recessive genetic models. We do not present, here, the results for the dominant or recessive models because they did not contribute meaningfully to the results. However, to implement more flexible analyses, such as parent-of-origin analyses, we also used an in-house program written for family-based association (49) that implements methods described by Cordell et al. (50). Comparisons of the in-house program to FBAT results, when appropriate, yielded excellent agreement (unpublished data). A priori, we planned four principal analyses, all under the additive model: spectrum versus strict diagnosis by all ancestries versus European ancestry. These four analyses covered the extremes of phenotype and ancestry. Numerous exploratory analyses were also performed under an additive genetic model: parent of origin analysis considering paternal- and maternal-specific transmissions for both strict and spectrum diagnostic classes; and for the largest, spectrum sets, we stratified by proband's verbal/non-verbal status (51).
