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

H. Fridman, H.G. Yntema, R. Magi, R. Andreson, A. Metspalu, M. Mezzavila, C. Tyler-Smith, Y.L. Xue, S. Carmi, E. Levy-Lahad, C. Gilissen*, H.G. Brunner*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)608-619
Number of pages12
JournalAmerican Journal of Human Genetics
Issue number4
Publication statusPublished - 1 Apr 2021



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