Common variation in meiosis genes shapes human recombination phenotypes and aneuploidy risk

The leading cause of human pregnancy loss is aneuploidy, often tracing to errors in chromosome segregation during female meiosis^1,2. Although abnormal crossover recombination is known to confer risk for aneuploidy^3–6, limited data have hindered understanding of the potential shared genetic basis of these key molecular phenotypes. To address this gap, we performed retrospective analysis of preimplantation genetic testing data from 139,416in vitrofertilized embryos from 22,850 sets of biological parents. By tracing transmission of haplotypes, we identified 3,656,198 crossovers, as well as 92,485 aneuploid chromosomes. Counts of crossovers were lower in aneuploid versus euploid embryos, consistent with their role in chromosome pairing and segregation. Our analyses further revealed that a common haplotype spanning the meiotic cohesinSMC1Bis significantly associated with both crossover count and maternal meiotic aneuploidy, with evidence supporting a non-codingcis-regulatory mechanism. Transcriptome- and phenome-wide association tests also implicated variation in the synaptonemal complex componentC14orf39and crossover-regulating ubiquitin ligasesCCNB1IP1andRNF212in meiotic aneuploidy risk. More broadly, recombination and aneuploidy possess a partially shared genetic basis that also overlaps with reproductive aging traits. Our findings highlight the dual role of recombination in generating genetic diversity, while ensuring meiotic fidelity.