Fig. 1. One challenge of biomarker research in a clinical population, such as patients with a specific neurodevelopmental diagnosis (e.g., ASD or schizophrenia), is the underlying etiological heterogeneity (different colored circles).

Theoretically, extracting a subset of patients based on a shared genetic origin (red circles only) such as 22q11DS, could reduce heterogeneity, thereby improving the ability to detect meaningful biomarker signals. Notable examples include the highly reproducible neuroanatomic signature of 22q11DS-associated psychosis [169, 156, 159], and emerging evidence for distinguishable ASD profiles in subgroups of individuals with ASD according to genetic etiology [170–173]. Examples of reduced heterogeneity in genetically selected subsets of patients are also observed in other genetic conditions; for example, distinctive electrophysiological brain wave patterns observed in children with ASD related to the 15q11.2-q13.2 duplication compared to children with idiopathic ASD [174], and macrocephaly and gastrointestinal problems in children with ASD related to mutations in CHD8 [175].