Matches in SemOpenAlex for { <https://semopenalex.org/work/W2899589929> ?p ?o ?g. }
- W2899589929 abstract "Large exome-sequencing datasets offer an unprecedented opportunity to understand the genetic architecture of rare diseases, informing clinical genetics counseling and optimal study designs for disease gene identification. We analyzed 7,448 exome-sequenced families from the Deciphering Developmental Disorders study, and, for the first time, estimated the causal contribution of recessive coding variation exome-wide. We found that the proportion of cases attributable to recessive coding variants is surprisingly low in patients of European ancestry, at only 3.6%, versus 50% of cases explained by de novo coding mutations. Surprisingly, we found that, even in European probands with affected siblings, recessive coding variants are only likely to explain ~12% of cases. In contrast, they account for 31% of probands with Pakistani ancestry due to elevated autozygosity. We tested every gene for an excess of damaging homozygous or compound heterozygous genotypes and found three genes that passed stringent Bonferroni correction: EIF3F , KDM5B , and THOC6 . EIF3F is a novel disease gene, and KDM5B has previously been reported as a dominant disease gene. KDM5B appears to follow a complex mode of inheritance, in which heterozygous loss-of-function variants (LoFs) show incomplete penetrance and biallelic LoFs are fully penetrant. Our results suggest that a large proportion of undiagnosed developmental disorders remain to be explained by other factors, such as noncoding variants and polygenic risk." @default.
- W2899589929 created "2018-11-16" @default.
- W2899589929 creator A5003253214 @default.
- W2899589929 creator A5003403293 @default.
- W2899589929 creator A5013429820 @default.
- W2899589929 creator A5013440996 @default.
- W2899589929 creator A5014189662 @default.
- W2899589929 creator A5016108750 @default.
- W2899589929 creator A5023547748 @default.
- W2899589929 creator A5025192393 @default.
- W2899589929 creator A5028653675 @default.
- W2899589929 creator A5039101004 @default.
- W2899589929 creator A5039170751 @default.
- W2899589929 creator A5040119863 @default.
- W2899589929 creator A5049698135 @default.
- W2899589929 creator A5053348744 @default.
- W2899589929 creator A5055650452 @default.
- W2899589929 creator A5059660178 @default.
- W2899589929 creator A5063847611 @default.
- W2899589929 creator A5066551611 @default.
- W2899589929 creator A5068328021 @default.
- W2899589929 creator A5068997042 @default.
- W2899589929 creator A5069971095 @default.
- W2899589929 creator A5073448163 @default.
- W2899589929 creator A5073670384 @default.
- W2899589929 creator A5075816415 @default.
- W2899589929 creator A5076567939 @default.
- W2899589929 creator A5078901635 @default.
- W2899589929 creator A5080957965 @default.
- W2899589929 creator A5082143264 @default.
- W2899589929 creator A5082672179 @default.
- W2899589929 creator A5088355671 @default.
- W2899589929 creator A5091144355 @default.
- W2899589929 creator A5091717442 @default.
- W2899589929 date "2017-10-13" @default.
- W2899589929 modified "2023-10-18" @default.
- W2899589929 title "Quantifying the contribution of recessive coding variation to developmental disorders" @default.
- W2899589929 cites W1839370049 @default.
- W2899589929 cites W1872141876 @default.
- W2899589929 cites W1965582988 @default.
- W2899589929 cites W1976298213 @default.
- W2899589929 cites W1984037038 @default.
- W2899589929 cites W1987217465 @default.
- W2899589929 cites W1992641408 @default.
- W2899589929 cites W1993564909 @default.
- W2899589929 cites W1997587039 @default.
- W2899589929 cites W2008627757 @default.
- W2899589929 cites W2009313095 @default.
- W2899589929 cites W2012361142 @default.
- W2899589929 cites W2021035407 @default.
- W2899589929 cites W2029648614 @default.
- W2899589929 cites W2049020090 @default.
- W2899589929 cites W2054659582 @default.
- W2899589929 cites W2055502678 @default.
- W2899589929 cites W2082435050 @default.
- W2899589929 cites W2087216143 @default.
- W2899589929 cites W2088094902 @default.
- W2899589929 cites W2088737679 @default.
- W2899589929 cites W2096019836 @default.
- W2899589929 cites W2096128035 @default.
- W2899589929 cites W2100407705 @default.
- W2899589929 cites W2100493977 @default.
- W2899589929 cites W2104549677 @default.
- W2899589929 cites W2104787181 @default.
- W2899589929 cites W2108994842 @default.
- W2899589929 cites W2112313406 @default.
- W2899589929 cites W2119044832 @default.
- W2899589929 cites W2119228812 @default.
- W2899589929 cites W2121619206 @default.
- W2899589929 cites W2122092305 @default.
- W2899589929 cites W2127857992 @default.
- W2899589929 cites W2133404976 @default.
- W2899589929 cites W2138014988 @default.
- W2899589929 cites W2138196920 @default.
- W2899589929 cites W2144998676 @default.
- W2899589929 cites W2151114041 @default.
- W2899589929 cites W2154909271 @default.
- W2899589929 cites W2157752701 @default.
- W2899589929 cites W2157970897 @default.
- W2899589929 cites W2158266834 @default.
- W2899589929 cites W2161241553 @default.
- W2899589929 cites W2169348900 @default.
- W2899589929 cites W2231185426 @default.
- W2899589929 cites W2256016639 @default.
- W2899589929 cites W2263875137 @default.
- W2899589929 cites W2277462866 @default.
- W2899589929 cites W2336702220 @default.
- W2899589929 cites W2336716466 @default.
- W2899589929 cites W2345881696 @default.
- W2899589929 cites W2402942859 @default.
- W2899589929 cites W2417483443 @default.
- W2899589929 cites W2489911374 @default.
- W2899589929 cites W2518901523 @default.
- W2899589929 cites W2537623931 @default.
- W2899589929 cites W2551102722 @default.
- W2899589929 cites W2581649032 @default.
- W2899589929 cites W2591851215 @default.
- W2899589929 cites W2611476410 @default.
- W2899589929 cites W2637381607 @default.
- W2899589929 cites W2743391445 @default.