RESEARCH Testing for association of

Full list of author information is available at the end of the articleBackground Autism is a behaviorally defined syndrome characterized by extensive phenotypic variation and etiological hetero-geneity. Symptom constellations, disease severity, and as-sociated biological traits can differ markedly from one affected individual to another. This is true even in cases attributable to single genetic defects such as chromosome 15q11-13 duplications [1] or 16p11.2 deletions [2]. Based on heritability studies, while some phenotypic variability may be due to environmental factors, a substantial portion can be attributed to heritable ‘modifying ’ factors that have little effect on disease risk itself [3-5]. Identifying and studying modifying genes can be import-ant clinically. In hypertension, for example, common vari-ation in the renal NaCl-transporter SLC12A3 (NCCT) gene, while only minimally associated with disease, is strongly associated with biological traits related to bloo