Prioritizing embryos with lower homozygosity is expected to reduce disease risk in children of related individuals undergoing preimplantation genetic testing

Consanguinity is a reproductive union between individuals who share a recent common ancestor. These unions are common in many regions of the world and increase the burden of rare recessive disorders by elevating autozygosity in offspring. Current reproductive genetic screening focuses on a limited set of known pathogenic variants, leaving most recessive risk unaddressed. Here we argue that embryo-level autozygosity, quantified as the fraction of the genome in long runs of homozygosity ( F _ROH ), is a potentially actionable genomic biomarker that can be integrated into routine preimplantation genetic testing as a homozygosity-informed embryo-prioritization framework (PGT-H) that can be layered onto existing embryo biopsy workflows when couples are already undergoing IVF with PGT-A or PGT-M. Using forward simulations of first-cousin and double-first-cousin couples, we show that siblings conceived by the same couple span a wide range of F _ROH ; selecting the lowest- F _ROH candidate from a cohort of five embryos reduces F _ROH by approximately 40% on average. Combining these reductions with empirical effect-size estimates, we estimate that for first-cousin couples this strategy could reduce risk of intellectual disability by roughly 35 – 45% (corresponding to an absolute risk reduction of about 1.8 – 2.2%) and potentially reduce excess recessive disease burden, while also modestly reducing risk of common diseases such as type 2 diabetes. We outline how existing PGT-A and PGT-M workflows could potentially be extended to report embryo-level F _ROH and discuss ethical and counseling considerations. Autozygosity-based embryo prioritization offers a principled way to address a component of recessive risk that current variant-centric approaches miss.