The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects

The number and distribution of recessive alleles in the population for various diseases are not known at genome-wide-scale. Based on 6,447 exome sequences of healthy, genetically unrelated Europeans of two distinct ancestries, we estimate that every individual is a carrier of at least 2 pathogenic variants in currently known autosomal-recessive (AR) genes and that 0.8%-1% of European couples are at risk of having a child affected with a severe AR genetic disorder. This risk is 16.5-fold higher for first cousins but is significantly more increased for skeletal disorders and intellectual disabilities due to their distinct genetic architecture.

Automated summary

Genome sequencing revealed that each individual in the European population carries at least 2 pathogenic variants, with nearly 1% of European couples facing the risk of having a child with a severe genetic disorder. The risk is significantly higher for first cousins and particularly increased for skeletal disorders and intellectual disabilities due to their unique genetic architecture.