Abstract：
:To characterize the role of rare complete human knockouts in autism spectrum disorders (ASDs), we identify genes with homozygous or compound heterozygous loss-of-function (LoF) variants (defined as nonsense and essential splice sites) from exome sequencing of 933 cases and 869 controls. We identify a 2-fold increase in complete knockouts of autosomal genes with low rates of LoF variation (≤ 5% frequency) in cases and estimate a 3% contribution to ASD risk by these events, confirming this observation in an independent set of 563 probands and 4,605 controls. Outside the pseudoautosomal regions on the X chromosome, we similarly observe a significant 1.5-fold increase in rare hemizygous knockouts in males, contributing to another 2% of ASDs in males. Taken together, these results provide compelling evidence that rare autosomal and X chromosome complete gene knockouts are important inherited risk factors for ASD.
journal_name
Neuronjournal_title
Neuronauthors
Lim ET,Raychaudhuri S,Sanders SJ,Stevens C,Sabo A,MacArthur DG,Neale BM,Kirby A,Ruderfer DM,Fromer M,Lek M,Liu L,Flannick J,Ripke S,Nagaswamy U,Muzny D,Reid JG,Hawes A,Newsham I,Wu Y,Lewis L,Dinh H,Gross S,Wdoi
10.1016/j.neuron.2012.12.029subject
Has Abstractpub_date
2013-01-23 00:00:00pages
235-42issue
2eissn
0896-6273issn
1097-4199pii
S0896-6273(13)00033-0journal_volume
77pub_type
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