Threshold for neural tube defect risk by accumulated singleton loss-of-function variants
Dear Editor,Neural tube defects (NTDs) are a class of major structural malformations affecting the brain and spinal cord.They are among the most common congenital anomalies with a worldwide prevalence of 0.1％.1,2 Elucidating the genetic basis of their complex etiology has eluded our best efforts to date.Although there are more than 400 genes capable of producing an NTD phenotype when mutated in the mouse,3,4 studies of human candidate genes based on mouse NTD genes have not been informative,except for genes in the planar cell polarity pathway.5 Recently,an omnigenic model of inheritance was proposed for complex traits,suggesting that the associated signals tend to spread across almost the entire genome.6 In light of this new perspective on the genomic architecture of complex traits,we re-evaluated whole-genome sequencing (WGS) data from three different NTD cohorts (Han Chinese,Caucasian USA,and Middle Eastern/Qatar).
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We thank the families for their participation in this study.Data analysis and computing resource were supported by Center for Big Data Research in Health,Institute of Biophysics,Chinese Academy of Sciences.This project was supported by the National Key Basic Research Program of China2016YFC1000502;the National Natural Science Foundation of China81430005,31521003,31771669,81741048;the Commission for Science and Technology of Shanghai Municipality 17JC1400902 to H.W.and Y.Z;NIH HD081216,HD083809,and HD067244 to R.H.F.and M.E.R
2018-11-22（万方平台首次上网日期，不代表论文的发表时间）
共3页
1039-1041
