Runs of Homozygosity Predict Inbreeding Depression Across Taxa: A Systematic Review and Meta-Analysis

Measuring inbreeding via runs of homozygosity (ROH) captures realized autozygosity and can infer inbreeding timing through ROH length. A growing body of literature links the proportion of the genome in ROH (F_ROH) to fitness outcomes across taxa, yet systematic synthesis has been lacking. Here, we conduct a systematic review and meta-analysis to quantify F_ROH-fitness associations, identify drivers of variation and derive conservation-relevant recommendations. Narrative synthesis of 44 studies revealed that inbreeding depression operates through multiple interconnected pathways (survival, maternal effects, disease susceptibility, reproduction). Critically, purging cannot be relied upon to eliminate inbreeding depression as substantial fitness costs persist even in historically small populations. Meta-analysis of 62 effect sizes revealed a significant negative association between genomic inbreeding and fitness across taxa (Fisher's z = -0.103, r = -0.10, p < 0.0001). Study group, whether wildlife, livestock or humans, explained 22.5% of variance, with wildlife showing strongest effects (6-fold stronger than humans). Survival traits showed the greatest sensitivity to the effects of ROH (r = -0.22). Additionally, ROH detection methodology significantly influenced effect sizes: comprehensive approaches (all ROH lengths) detected stronger depression (r = -0.18) than long-ROH-only analyses (r = -0.08, p = 0.008), indicating cumulative genetic load matters. Overall, results indicate significant but variable fitness associations with ROH, with effect magnitude depending on biological context and methodological approach. Comprehensive ROH-based approaches show promise as conservation monitoring tools, but limited wildlife studies, particularly for non-mammalian taxa, highlight an urgent need for standardized protocols and expanded empirical research.