Quantifying the contribution of recessive coding variation to developmental disorders

Deciphering Developmental Disorders Study

Research output: Contribution to journalArticlepeer-review


We estimated the genome-wide contribution of recessive coding variation from 6,040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared to 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, due to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, KDM5B and EIF3F, and functionally validated them with mouse and cellular models. Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed non-consanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.

Original languageEnglish
Early online date8 Nov 2018
Publication statusPublished - 7 Dec 2018


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