A convergent molecular network underlying autism and congenital heart disease.
A convergent molecular network underlying autism and congenital heart disease.
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DOI：
10.1016/j.cels.2021.07.009
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发表时间：
2021-11-17
期刊：
影响因子：
9.3
通讯作者：
Ideker T
中科院分区：
文献类型：
--
作者：
Rosenthal SB;Willsey HR;Xu Y;Mei Y;Dea J;Wang S;Curtis C;Sempou E;Khokha MK;Chi NC;Willsey AJ;Fisch KM;Ideker T
Patients with neurodevelopmental disorders, including autism, have an elevated incidence of congenital heart disease, but the extent to which these conditions share molecular mechanisms remains unknown. Here we use network genetics to identify a convergent molecular network underlying autism and congenital heart disease. This network is impacted by damaging genetic variants from both disorders in multiple independent cohorts of patients, pinpointing 101 genes with shared genetic risk. Network analysis also implicates risk genes for each disorder separately, including 27 previously unidentified genes for autism and 46 for congenital heart disease. For 7 genes with shared risk, we create engineered disruptions in Xenopus tropicalis, confirming both heart and brain developmental abnormalities. The network includes a family of ion channels, such as the sodium transporter SCN2A, linking these functions to early heart and brain development. This study provides a roadmap for identifying risk genes and pathways involved in co-morbid conditions. Rosenthal et al. use network genetics to identify a convergent molecular network underlying autism and congenital heart disease, two co-morbid disorders. This network is impacted by damaging genetic variants from both disorders in multiple independent cohorts of patients, pinpointing 101 genes with shared genetic risk. The network implicates a large family of ion channels, including the sodium transporter SCN2A, in which the authors show disruptions cause defects in Xenopus heart and brain development.
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影响因子：
30.8
作者：
Doan, Ryan N.;Lim, Elaine T.;Yu, Timothy W.
通讯作者：
Yu, Timothy W.
影响因子：
--
作者：
Garfinkel AM;Khokha MK
通讯作者：
Khokha MK
影响因子：
14.9
作者：
Brinkman EK;Chen T;Amendola M;van Steensel B
通讯作者：
van Steensel B
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
4.5
作者：
Ben-David E;Shifman S
通讯作者：
Shifman S