Handedness in the Broader Autism Phenotype: A Systematic Review and Meta-Analysis

Atypical handedness (i.e., non-right-handedness, left-handedness, and mixed-handedness) has been repeatedly associated with autism spectrum disorder (ASD) and is thought to reflect underlying atypicalities in functional cerebral lateralization. The broader autism phenotype (BAP), encompassing subclinical traits of ASD observed more frequently in first-degree relatives of individuals with ASD, may similarly exhibit altered lateralization patterns. However, no systematic synthesis of evidence on atypical handedness in BAP currently exists. This registered report outlines the protocol for a systematic review and meta-analysis investigating the hypothesis of a higher prevalence of atypical handedness in the BAP relative to neurotypical controls. Following PRISMA 2020 guidelines, we will conduct comprehensive searches of PubMed, Scopus, and PsycInfo. Eligible studies will (i) report handedness data for individuals identified as BAP, (ii) include a neurotypical comparison group, and (iii) not have selected participants based on handedness. Three handedness classifications will be examined: non-right-handedness, left-handedness, and mixed-handedness. For each classification, random-effects meta-analyses will be used to compute pooled odds ratios. Results will be visualized using forest plots and drapery plots. Between-study heterogeneity will be quantified using Cochran’s Q and the I² statistic, and potential moderators (e.g., age, sex, handedness measure, BAP classification) will be examined. Sensitivity analyses will assess robustness, and small-study bias will be tested via Egger’s test and funnel plots, complemented by exploratory Bayesian publication bias tests. Establishing this association will inform theoretical models of neurodevelopment and cerebral lateralization, and support the identification of non-invasive behavioral markers for subclinical autistic traits.